Histone deacetylase inhibitors

ABSTRACT

Compounds, pharmaceutical compositions, kits and methods are provided for use with HDAC that comprise a compound selected from the group consisting of:  
                 
wherein the substituents are as defined herein.

RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application No.60/699,139, filed Jul. 14, 2005, which is incorporated herein byreference.

FIELD OF THE INVENTION

The present invention relates to compounds that may be used to inhibithistone deacetylases (HDACs), as well as compositions of matter and kitscomprising these compounds. The invention also relates to methods forinhibiting HDACs and treatment methods using compounds according to thepresent invention. In particular, the present invention relates tocompounds, compositions of matter, kits and methods used to inhibitClass I HDACs, such as HDAC1, HDAC2, HDAC6 and HDAC8.

BACKGROUND OF THE INVENTION

DNA in eukaryotic cells is tightly complexed with proteins (histones) toform chromatin. Histones are small, positively charged proteins that arerich in basic amino acids (positively charged at physiological pH),which contact the phosphate groups (negatively charged at physiologicalpH) of DNA. There are five main classes of histones H1, H2A, H2B, H3,and H4. The amino acid sequences of H2A, H2B, H3, and H4 show remarkableconservation between species, wherein H1 varies somewhat and in somecases is replaced by another histone, e.g., H5. Four pairs of each ofH2A, H2B, H3 and H4 together form a disk-shaped octomeric protein core,around which DNA (about 140 base pairs) is wound to form a nucleosome.Individual nucleosomes are connected by short stretches of linker DNAassociated with another histone molecule to form a structure resemblinga beaded string, which is itself arranged in a helical stack, known as asolenoid.

The majority of histones are synthesized during the S phase of the cellcycle, and newly synthesized histones quickly enter the nucleus tobecome associated with DNA. Within minutes of its synthesis, new DNAbecomes associated with histones in nucleosomal structures.

A small fraction of histones, more specifically, the amino acid sidechains thereof, are enzymatically modified by post-translationaladdition of methyl, acetyl, or phosphate groups, neutralizing thepositive charge of the side chain, or converting it to a negativecharge. For example, lysine and arginine groups may be methylated,lysine groups may be acetylated, and serine groups may bephosphorylated. For lysine, the —(CH₂)₄—NH₂ sidechain may be acetylated,for example by an acetyltransferase enzyme to give the amide—(CH₂)₄—NHC(═O)CH₃. Methylation, acetylation, and phosphorylation ofamino termini of histones that extend from the nucleosomal core affectschromatin structure and gene expression. Spencer and Davie 1999. Gene240:11-12.

Acetylation and deacetylation of histones is associated withtranscriptional events leading to cell proliferation and/ordifferentiation. Regulation of the function of transcriptional factorsis also mediated through acetylation. Recent reviews on histonedeacetylation include Kouzarides et al., 1999, Curr. Opin. Genet. Dev.9:1, 40-48 and Pazin et al., 1997, 89:3 325-328.

The correlation between acetylation status of histones and thetranscription of genes has been known for quite some time. Certainenzymes, specifically acetylases (e.g., histone acetyltransferases (HAT)and deacetylases (histone deacetylases or HDACs), which regulate theacetylation state of histones have been identified in many organisms andhave been implicated in the regulation of numerous genes, confirming alink between acetylation and transcription. In general, histoneacetylation is believed to correlate with transcriptional activation,whereas histone deacetylation is believed to be associated with generepression.

A growing number of histone deacetylases (HDACs) have been identified.HDACs function as part of large multiprotein complexes, which aretethered to the promoter and repress transcription. Well characterizedtranscriptional repressors such as MAD, nuclear receptors and YY1associate with HDAC complexes to exert their repressor function.

Studies of HDAC inhibitors have shown that these enzymes play animportant role in cell proliferation and differentiation. HDACs arebelieved to be associated with a variety of different disease statesincluding, but not limited to cell proliferative diseases and conditions(Marks, P. A., Richon, V. M., Breslow, R. and Rifkind, R. A., J. Natl.Cancer Inst. (Bethesda) 92, 1210-1215, 2000) such as leukemia (Lin etal., 1998. Nature 391: 811-814; Grignani et al.1998. Nature 391:815-818; Warrell et al., 1998, J. Natl. Cancer Inst. 90:1621-1625;Gelmetti et al., 1998, Mol. Cell Biol. 18:7185-7191; Wang et al., 1998,PNAS 951 0860-10865), melanomas/squamous cell carcinomas (Gillenwater etal., 1998, Int. J. Cancer 75217-224; Saunders et al., 1999, Cancer Res.59:399-404), breast cancer, prostrate cancer, bladder cancer (Gelmettiet al., 1998, Mol. Cell Biol. 18:7185-7191; Wang et al., 1998, PNAS 9510860-10865), lung cancer, ovarian cancer, colon cancer (Hassig et al.,1997, Chem. Biol. 4:783-789; Archer et al., 1998, PNAS, 956791-6796;Swendeman et al., 1999, Proc. Amer. Assoc. Cancer Res. 40, Abstract#3836), and hyperproliferative skin disease such as cancerous andprecancerous skin lesions, as well as inflammatory cutaneous disorders.

Histone deacetylase inhibitors are potent inducers of growth arrest,differentiation, or apoptotic cell death in a variety of transformedcells in culture and in tumor bearing animals (Histone deacetylaseinhibitors as new cancer drugs, Marks, P. A., Richon, V. M., Breslow, R.and Rifkind, R. A., Current Opinions in Oncology, 2001, Nov. 13 (6):477-83; Histone deacetylases and cancer: causes and therapies, Marks,P., Rifkind, R. A., Richon, V. M., Breslow, R., Miller, T. and Kelly, W.K., Nat. Rev. Cancer Dec. 1, 2001 (3):194-202). In addition, HDACinhibitors are useful in the treatment or prevention of protozoaldiseases (U.S. Pat. No. 5,922,837) and psoriasis (PCT Publication No. WO02/26696).

Accordingly, despite the various HDAC inhibitors that have been reportedto date, a need continues to exist for new and more effective inhibitorsof HDACs.

SUMMARY OF THE INVENTION

The present invention relates to compounds that have activity forinhibiting histone deacetylases (HDACs). The present invention alsoprovides compositions, articles of manufacture and kits comprising thesecompounds.

In one embodiment, a pharmaceutical composition is provided thatcomprises an HDAC inhibitor according to the present invention as anactive ingredient. Pharmaceutical compositions according to theinvention may optionally comprise 0.001%-100% of one or more HDACinhibitors of this invention. These pharmaceutical compositions may beadministered or coadministered by a wide variety of routes, includingfor example, orally, parenterally, intraperitoneally, intravenously,intraarterially, transdermally, sublingually, intramuscularly, rectally,transbuccally, intranasally, liposomally, via inhalation, vaginally,intraoccularly, via local delivery (for example by catheter or stent),subcutaneously, intraadiposally, intraarticularly, or intrathecally. Thecompositions may also be administered or co-administered in slow releasedosage forms.

The invention is also directed to kits and other articles of manufacturefor treating disease states associated with one or more HDAC.

In one embodiment, a kit is provided that comprises a compositioncomprising at least one HDAC inhibitor of the present invention incombination with instructions. The instructions may indicate the diseasestate for which the composition is to be administered, storageinformation, dosing information and/or instructions regarding how toadminister the composition. The kit may also comprise packagingmaterials. The packaging material may comprise a container for housingthe composition. The kit may also optionally comprise additionalcomponents, such as syringes for administration of the composition. Thekit may comprise the composition in single or multiple dose forms.

In another embodiment, an article of manufacture is provided thatcomprises a composition comprising at least one HDAC inhibitor of thepresent invention in combination with packaging materials. The packagingmaterial may comprise a container for housing the composition. Thecontainer may optionally comprise a label indicating the disease statefor which the composition is to be administered, storage information,dosing information and/or instructions regarding how to administer thecomposition. The kit may also optionally comprise additional components,such as syringes for administration of the composition. The kit maycomprise the composition in single or multiple dose forms.

Also provided are methods for preparing compounds, compositions and kitsaccording to the present invention. For example, several syntheticschemes are provided herein for synthesizing compounds according to thepresent invention. In still another embodiment, reactive intermediatesare provided for use in conjunction with the synthetic schemes.

Also provided are methods for using compounds, compositions, kits andarticles of manufacture according to the present invention.

In one embodiment, the compounds, compositions, kits and articles ofmanufacture are used to inhibit one or more HDAC.

In another embodiment, the compounds, compositions, kits and articles ofmanufacture are used to treat a disease state for which one or more HDACpossesses activity that contributes to the pathology and/or symptomologyof the disease state.

In another embodiment, a compound is administered to a subject whereinHDAC activity within the subject is altered, preferably reduced.

In another embodiment, a prodrug of a compound is administered to asubject that is converted to the compound in vivo where it inhibits oneor more HDAC.

In another embodiment, a method of inhibiting one or more HDAC isprovided that comprises contacting an HDAC with a compound according tothe present invention.

In another embodiment, a method of inhibiting one or more HDAC isprovided that comprises causing a compound according to the presentinvention to be present in a subject in order to inhibit the HDAC invivo.

In another embodiment, a method of inhibiting an HDAC is provided thatcomprises administering a first compound to a subject that is convertedin vivo to a second compound wherein the second compound inhibits theHDAC in vivo. It is noted that the compounds of the present inventionmay be the first or second compounds.

In another embodiment, a therapeutic method is provided that comprisesadministering a compound according to the present invention.

In another embodiment, a method of treating a condition in a patientwhich is known to be mediated by one or more HDAC, or which is known tobe treated by HDAC inhibitors, comprising administering to the patient atherapeutically effective amount of a compound according to the presentinvention.

In another embodiment, a method is provided for treating a disease statefor which one or more HDAC possesses activity that contributes to thepathology and/or symptomology of the disease state, the methodcomprising: causing a compound according to the present invention to bepresent in a subject in a therapeutically effective amount for thedisease state.

In another embodiment, a method is provided for treating a disease statefor which one or more HDAC possesses activity that contributes to thepathology and/or symptomology of the disease state, the methodcomprising: administering a first compound to a subject that isconverted in vivo to a second compound such that the second compound ispresent in the subject in a therapeutically effective amount for thedisease state. It is noted that the compounds of the present inventionmay be the first or second compounds.

In another embodiment, a method is provided for treating a disease statefor which one or more HDAC possesses activity that contributes to thepathology and/or symptomology of the disease state, the methodcomprising: administering a compound according to the present inventionto a subject such that the compound is present in the subject in atherapeutically effective amount for the disease state.

In another embodiment, a method is provided for using a compoundaccording to the present invention in order to manufacture a medicamentfor use in the treatment of a disease state that is known to be mediatedby one or more HDAC, or that is known to be treated by HDAC inhibitors.

It is noted in regard to all of the above embodiments that the presentinvention is intended to encompass all pharmaceutically acceptableionized forms (e.g., salts) and solvates (e.g., hydrates) of thecompounds, regardless of whether such ionized forms and solvates arespecified since it is well know in the art to administer pharmaceuticalagents in an ionized or solvated form. It is also noted that unless aparticular stereochemistry is specified, recitation of a compound isintended to encompass all possible stereoisomers (e.g., enantiomers ordiastereomers depending on the number of chiral centers), independent ofwhether the compound is present as an individual isomer or a mixture ofisomers. Further, unless otherwise specified, recitation of a compoundis intended to encompass all possible resonance forms and tautomers.With regard to the claims, the language “compound comprising theformula” is intended to encompass the compound and all pharmaceuticallyacceptable ionized forms and solvates, all possible stereoisomers, andall possible resonance forms and tautomers unless otherwise specificallyspecified in the particular claim.

It is further noted that prodrugs may also be administered which arealtered in vivo and become a compound according to the presentinvention. The various methods of using the compounds of the presentinvention are intended, regardless of whether prodrug delivery isspecified, to encompass the administration of a prodrug that isconverted in vivo to a compound according to the present invention. Itis also noted that certain compounds of the present invention may bealtered in vivo prior to inhibiting kinases and thus may themselves beprodrugs for another compound. Such prodrugs of another compound may ormay not themselves independently have kinase inhibitory activity.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates residues 1-482 of HDAC1 and a Flag tag at both the N—and C-terminus (SEQ ID NO: 1).

FIG. 2 illustrates the DNA sequence (SEQ ID NO: 2) that was used toencode SEQ ID NO: 1.

FIG. 3 illustrates residues 1-488 of HDAC2 and a 6-histidine tag at theC-terminus (SEQ ID NO: 3).

FIG. 4 illustrates the DNA sequence (SEQ ID NO: 4) that was used toencode SEQ ID NO: 3.

FIG. 5 illustrates residues 73-845 of HDAC6 and a 6-histidine tag at theC-terminus (SEQ ID NO: 5).

FIG. 6 illustrates the DNA sequence (SEQ ID NO: 6) that was used toencode SEQ ID NO: 5.

FIG. 7 illustrates residues 1-377 of HDAC8 and a 6-histidine tag at theN-terminus (SEQ ID NO: 7).

FIG. 8 illustrates the DNA sequence (SEQ ID NO: 8) that was used toencode SEQ ID NO: 7.

DEFINITIONS

Unless otherwise stated, the following terms used in the specificationand claims shall have the following meanings for the purposes of thisApplication.

“Alicyclic” means a moiety comprising a non-aromatic ring structure.Alicyclic moieties may be saturated or partially unsaturated with one,two or more double or triple bonds. Alicyclic moieties may alsooptionally comprise heteroatoms such as nitrogen, oxygen and sulfur. Thenitrogen atoms can be optionally quaternerized or oxidized and thesulfur atoms can be optionally oxidized. Examples of alicyclic moietiesinclude, but are not limited to moieties with C₃₋₈ rings such ascyclopropyl, cyclohexane, cyclopentane, cyclopentene, cyclopentadiene,cyclohexane, cyclohexene, cyclohexadiene, cycloheptane, cycloheptene,cycloheptadiene, cyclooctane, cyclooctene, and cyclooctadiene.

“Aliphatic” means a moiety characterized by a straight or branched chainarrangement of constituent carbon atoms and may be saturated orpartially unsaturated with one, two or more double or triple bonds.

“Alkoxy” means an oxygen moiety having a further alkyl substituent. Thealkoxy groups of the present invention can be optionally substituted.

“Alkyl” represented by itself means a straight or branched, saturated orunsaturated, aliphatic radical having a chain of carbon atoms,optionally with oxygen (See “oxaalkyl”) or nitrogen atoms (See“aminoalkyl”) between the carbon atoms. C_(X) alkyl and C_(X—Y) alkylare typically used where X and Y indicate the number of carbon atoms inthe chain. For example, C₁₋₆ alkyl includes alkyls that have a chain ofbetween 1 and 6 carbons (e.g., methyl, ethyl, propyl, isopropyl, butyl,sec-butyl, isobutyl, tert-butyl, vinyl, allyl, 1-propenyl, isopropenyl,1-butenyl, 2-butenyl, 3-butenyl, 2-methylallyl, ethynyl, 1-propynyl,2-propynyl, and the like). Alkyl represented along with another radical(e.g., as in arylalkyl, heteroarylalkyl) means a straight or branched,saturated or unsaturated aliphatic divalent radical having the number ofatoms indicated or when no atoms are indicated means a bond (e.g.,(C₆₋₁₀)aryl(C₁₋₃)alkyl includes, benzyl, phenethyl, 1-phenylethyl,3-phenylpropyl, 2-thienylmethyl, 2-pyridinylmethyl and the like).

“Alkenyl” means a straight or branched, carbon chain that contains atleast one carbon-carbon double bond. Examples of alkenyl include vinyl,allyl, isopropenyl, pentenyl, hexenyl, heptenyl, 1-propenyl, 2-butenyl,2-methyl-2-butenyl, and the like.

“Alkynyl” means a straight or branched, carbon chain that contains atleast one carbon-carbon triple bond. Examples of alkynyl includeethynyl, propargyl, 3-methyl-1-pentynyl, 2-heptynyl and the like.

“Alkylene”, unless indicated otherwise, means a straight or branched,saturated or unsaturated, aliphatic, divalent radical. C_(X) alkyleneand C_(X—Y) alkylene are typically used where X and Y indicate thenumber of carbon atoms in the chain. For example, C₁₋₆ alkylene includesmethylene (—CH₂—), ethylene (—CH₂CH₂—), trimethylene (—CH₂CH₂CH₂—),tetramethylene (—CH₂CH₂CH₂CH₂—) 2-butenylene (—CH₂CH═CHCH₂—),2-methyltetramethylene (—CH₂CH(CH₃)CH₂CH₂—), pentamethylene(—CH₂CH₂CH₂CH₂CH₂—) and the like.

“Alkenylene” means a straight or branched, divalent carbon chain havingone or more carbon-carbon double bonds. Examples of alkenylene includeethene-1,2-diyl, propene-1,3-diyl, methylene-1,1-diyl, and the like.

“Alkynylene” means a straight or branched, divalent carbon chain havingone or more carbon-carbon triple bonds. Examples of alkynylene includeethyne-1,2-diyl, propyne-1,3-diyl, and the like.

“Alkylidene” means a straight or branched saturated or unsaturated,aliphatic radical connected to the parent molecule by a double bond.C_(X) alkylidene and C_(X—Y) alkylidene are typically used where X and Yindicate the number of carbon atoms in the chain. For example, C₁₋₆alkylidene includes methylene (═CH₂), ethylidene (═CHCH₃),isopropylidene (═C(CH₃)₂), propylidene (═CHCH₂CH₃), allylidene(═CH—CH═CH₂), and the like).

“Amido” means the radical —NR_(a)C(O)R_(b) where the point of attachmentto the molecule is at the nitrogen, and R_(a) and R_(b) are furthersubstituents attached to the nitrogen and the carbon of the carbonyl,respectively.

“Amino” means a nitrogen moiety having two further substituents where,for example, a hydrogen or carbon atom is attached to the nitrogen. Forexample, representative amino groups include —NH₂, —NHCH₃, —N(CH₃)₂,—NHC₁₋₁₀alkyl, —N(C₁₋₁₀-alkyl)₂, —NHaryl, —NHheteroaryl, —N(aryl)₂,—N(heteroaryl)₂, and the like. Optionally, the two substituents togetherwith the nitrogen may also form a ring. Unless indicated otherwise, thecompounds of the invention containing amino moieties may includeprotected derivatives thereof. Suitable protecting groups for aminomoieties include acetyl, tert-butoxycarbonyl, benzyloxycarbonyl, and thelike.

“Aminoalkyl” means an alkyl, as defined above, except where one or moresubstituted or unsubstituted nitrogen atoms (—N—) are positioned betweencarbon atoms of the alkyl. For example, an (C₂₋₆) aminoalkyl refers to achain comprising between 2 and 6 carbons and one or more nitrogen atomspositioned between the carbon atoms.

“Animal” includes humans, non-human mammals (e.g., dogs, cats, rabbits,cattle, horses, sheep, goats, swine, deer, and the like) and non-mammals(e.g., birds, and the like).

“Aromatic” means a moiety wherein the constituent atoms make up anunsaturated ring system, all atoms in the ring system are sp² hybridizedand the total number of pi electrons is equal to 4n+2. An aromatic ringmay be such that the ring atoms are only carbon atoms or may includecarbon and non-carbon atoms (see Heteroaryl).

“Aryl” means a monocyclic or polycyclic ring assembly wherein each ringis aromatic or when fused with one or more rings forms an aromatic ringassembly. If one or more ring atoms is not carbon (e.g., N, S), the arylis a heteroaryl. C_(X) aryl and C_(X—Y) aryl are typically used where Xand Y indicate the number of atoms in the ring.

“Bicycloalkyl” means a saturated or partially unsaturated fused bicyclicor bridged polycyclic ring assembly.

“Bicycloaryl” means a bicyclic ring assembly wherein the rings arelinked by a single bond or fused and at least one of the ringscomprising the assembly is aromatic. C_(X) bicycloaryl and C_(X—Y)bicycloaryl are typically used where X and Y indicate the number ofcarbon atoms in the bicyclic ring assembly and directly attached to thering.

“Bridging ring” as used herein refers to a ring that is bonded toanother ring to form a compound having a bicyclic structure where tworing atoms that are common to both rings are not directly bound to eachother. Non-exclusive examples of common compounds having a bridging ringinclude borneol, norbornane, 7-oxabicyclo[2.2.1]heptane, and the like.One or both rings of the bicyclic system may also comprise heteroatoms.

“Carbamoyl” means the radical —OC(O)NR_(a)R_(b) where R_(a) and R_(b)are each independently two further substituents where a hydrogen orcarbon atom is attached to the nitrogen.

“Carbocycle” means a ring consisting of carbon atoms.

“Carbocyclic ketone derivative” means a carbocyclic derivative whereinthe ring contains a —CO— moiety.

“Carbonyl” means the radical —CO—. It is noted that the carbonyl radicalmay be further substituted with a variety of substituents to formdifferent carbonyl groups including acids, acid halides, aldehydes,amides, esters, and ketones.

“Carboxamido” means the radical —C(O)NR_(a)R_(b) where the point ofattachment to the molecule is at the carbon of the carbonyl, and R_(a)and R_(b) are each independently two further substituents on thenitrogen.

“Carboxy” means the radical —CO₂—. It is noted that compounds of theinvention containing carboxy moieties may include protected derivativesthereof, i.e., where the oxygen is substituted with a protecting group.Suitable protecting groups for carboxy moieties include benzyl,tert-butyl, and the like.

“Cyano” means the radical —CN.

“Cycloalkyl” means a non-aromatic, saturated or partially unsaturated,monocyclic, fused bicyclic or bridged polycyclic ring assembly. C_(X)cycloalkyl and C_(X—Y) cycloalkyl are typically used where X and Yindicate the number of carbon atoms in the ring assembly. For example,C₃₋₁₀ cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cyclohexenyl, 2,5-cyclohexadienyl, bicyclo[2.2.2]octyl,adamantan-1-yl, decahydronaphthyl, oxocyclohexyl, dioxocyclohexyl,thiocyclohexyl, 2-oxobicyclo [2.2.1]hept-1-yl, and the like.

“Cycloalkylene” means a divalent saturated or partially unsaturated,monocyclic or polycyclic ring assembly. C_(X) cycloalkylene and C_(X—Y)cycloalkylene are typically used where X and Y indicate the number ofcarbon atoms in the ring assembly.

“Disease” specifically includes any unhealthy condition of an animal orpart thereof and includes an unhealthy condition that may be caused by,or incident to, medical or veterinary therapy applied to that animal,i.e., the “side effects” of such therapy.

“Fused ring” as used herein refers to a ring that is bonded to anotherring to form a compound having a bicyclic structure when the ring atomsthat are common to both rings are directly bound to each other.Non-exclusive examples of common fused rings include decalin,naphthalene, anthracene, phenanthrene, indole, furan, benzofuran,quinoline, and the like. Compounds having fused ring systems may besaturated, partially saturated, carbocyclics, heterocyclics, aromatics,heteroaromatics, and the like.

“Halo” means fluoro, chloro, bromo or iodo.

“Halo-substituted alkyl”, as an isolated group or part of a largergroup, means “alkyl” substituted by one or more “halo” atoms, as suchterms are defined in this Application. Halo-substituted alkyl includeshaloalkyl, dihaloalkyl, trihaloalkyl, perhaloalkyl and the like (e.g.,halo-substituted (C₁₋₃)alkyl includes chloromethyl, dichloromethyl,difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, perfluoroethyl,2,2,2-trifluoro-1,1-dichloroethyl, and the like).

“Heteroatom” refers to an atom that is not a carbon atom. Particularexamples of heteroatoms include, but are not limited to nitrogen,oxygen, and sulfur.

“Heteroatom moiety” includes a moiety where the atom by which the moietyis attached is not a carbon. Examples of heteroatom moieties include—N═, —NR_(c)—, —N⁺(O⁻)═, —O—, —S— or —S(O)₂—, wherein R_(c) is furthersubstituent.

“Heterobicycloalkyl” means bicycloalkyl, as defined in this Application,provided that one or more of the atoms within the ring is a heteroatom.For example hetero(C₉₋₁₂)bicycloalkyl as used in this applicationincludes, but is not limited to, 3-aza-bicyclo[4.1.0]hept-3-yl,2-aza-bicyclo[3.1.0]hex-2-yl , 3-aza-bicyclo[3.1.0]hex-3-yl, and thelike.

“Heterocycloalkylene” means cycloalkylene, as defined in thisApplication, provided that one or more of the ring member carbon atomsis replaced by a heteroatom.

“Heteroaryl” means a cyclic aromatic group having five or six ringatoms, wherein at least one ring atom is a heteroatom and the remainingring atoms are carbon. The nitrogen atoms can be optionallyquaternerized and the sulfur atoms can be optionally oxidized.Heteroaryl groups of this invention include, but are not limited to,those derived from furan, imidazole, isothiazole, isoxazole, oxadiazole,oxazole, 1,2,3-oxadiazole, pyrazine, pyrazole, pyridazine, pyridine,pyrimidine, pyrroline, thiazole, 1,3,4-thiadiazole, triazole andtetrazole. “Heteroaryl” also includes, but is not limited to, bicyclicor tricyclic rings, wherein the heteroaryl ring is fused to one or tworings independently selected from the group consisting of an aryl ring,a cycloalkyl ring, a cycloalkenyl ring, and another monocyclicheteroaryl or heterocycloalkyl ring. These bicyclic or tricyclicheteroaryls include, but are not limited to, those derived frombenzo[b]furan, benzo[b]thiophene, benzimidazole, imidazo[4,5-c]pyridine,quinazoline, thieno[2,3-c]pyridine, thieno[3,2-b]pyridine,thieno[2,3-b]pyridine, indolizine, imidazo[1,2a]pyridine, quinoline,isoquinoline, phthalazine, quinoxaline, naphthyridine, quinolizine,indole, isoindole, indazole, indoline, benzoxazole, benzopyrazole,benzothiazole, imidazo[1,5-a]pyridine, pyrazolo[1,5-a]pyridine,imidazo[1,2-a]pyrimidine, imidazo [1,2-c]pyrimidine, imidazo[1,5-a]pyrimidine, imidazo[1,5-c]pyrimidine, pyrrolo[2,3-b]pyridine,pyrrolo[2,3-c]pyridine, pyrrolo[3,2-c]pyridine, pyrrolo[3,2-b]pyridine,pyrrolo[2,3-d]pyrimidine, pyrrolo[3,2-d]pyrimidine,pyrrolo[2,3-b]pyrazine, pyrazolo[1,5-a]pyridine,pyrrolo[1,2-b]pyridazine, pyrrolo[1,2-c]pyrimidine,pyrrolo[1,2-a]pyrimidine, pyrrolo[1,2-a]pyrazine, triazo[1,5-a]pyridine,pteridine, purine, carbazole, acridine, phenazine, phenothiazene,phenoxazine, 1,2-dihydropyrrolo[3,2,1-hi]indole, indolizine,pyrido[1,2-a]indole and 2(1H)-pyridinone. The bicyclic or tricyclicheteroaryl rings can be attached to the parent molecule through eitherthe heteroaryl group itself or the aryl, cycloalkyl, cycloalkenyl orheterocycloalkyl group to which it is fused. The heteroaryl groups ofthis invention can be substituted or unsubstituted.

“Heterobicycloaryl” means bicycloaryl, as defined in this Application,provided that one or more of the atoms within the ring is a heteroatom.For example, hetero(C₄₋₁₂)bicycloaryl as used in this Applicationincludes, but is not limited to, 2-amino-4-oxo-3,4-dihydropteridin-6-yl,tetrahydroisoquinolinyl, and the like.

“Heterocycloalkyl” means cycloalkyl, as defined in this Application,provided that one or more of the atoms forming the ring is a heteroatomselected, independently from N, O, or S. Non-exclusive examples ofheterocycloalkyl include piperidyl, 4-morpholyl, 4-piperazinyl,pyrrolidinyl, perhydropyrrolizinyl, 1,4-diazaperhydroepinyl,1,3-dioxanyl, 1,4-dioxanyl and the like.

“Hydroxy” means the radical —OH.

“IC₅₀” means the molar concentration of an inhibitor that produces 50%inhibition of the target enzyme.

“Iminoketone derivative” means a derivative comprising the moiety—C(NR)—, wherein R comprises a hydrogen or carbon atom attached to thenitrogen.

“Isomers” mean any compound having an identical molecular formulae butdiffering in the nature or sequence of bonding of their atoms or in thearrangement of their atoms in space. Isomers that differ in thearrangement of their atoms in space are termed “stereoisomers.”Stereoisomers that are not mirror images of one another are termed“diastereomers” and stereoisomers that are nonsuperimposable mirrorimages are termed “enantiomers” or sometimes “optical isomers.” A carbonatom bonded to four nonidentical substituents is termed a “chiralcenter.” A compound with one chiral center has two enantiomeric forms ofopposite chirality. A mixture of the two enantiomeric forms is termed a“racemic mixture.” A compound that has more than one chiral center has2^(n−1) enantiomeric pairs, where n is the number of chiral centers.Compounds with more than one chiral center may exist as ether anindividual diastereomer or as a mixture of diastereomers, termed a“diastereomeric mixture.” When one chiral center is present astereoisomer may be characterized by the absolute configuration of thatchiral center. Absolute configuration refers to the arrangement in spaceof the substituents attached to the chiral center. Enantiomers arecharacterized by the absolute configuration of their chiral centers anddescribed by the R— and S-sequencing rules of Cahn, Ingold and Prelog.Conventions for stereochemical nomenclature, methods for thedetermination of stereochemistry and the separation of stereoisomers arewell known in the art (e.g., see “Advanced Organic Chemistry”, 4thedition, March, Jerry, John Wiley & Sons, New York, 1992).

“Leaving group” means a moiety that can be displaced by another moiety,such as by nucleophilic attack, during a chemical reaction. Leavinggroups are well known in the art and include, for example, halides andOSO₂R′ where R′ is, for example, alkyl, haloalkyl, or aryl optionallysubstituted by halo, alkyl, alkoxy, amino, and the like. Non-limitingexamples of leaving groups include chloro, bromo, iodo, mesylate,tosylate, and other similar groups.

“Nitro” means the radical —NO₂.

“Oxo” means the radical ═O.

“Oxaalkyl” means an alkyl, as defined above, except where one or moreoxygen atoms (—O—) are positioned between carbon atoms of the alkyl. Forexample, an (C₂₋₆)oxaalkyl refers to a chain comprising between 2 and 6carbons and one or more oxygen atoms positioned between the carbonatoms.

“Oxoalkyl” means an alkyl, further substituted with a carbonyl group.The carbonyl group may be an aldehyde, ketone, ester, amide, acid oracid chloride.

“Pharmaceutically acceptable” means that which is useful in preparing apharmaceutical composition that is generally safe, non-toxic and neitherbiologically nor otherwise undesirable and includes that which isacceptable for veterinary use as well as human pharmaceutical use.

“Pharmaceutically acceptable salts” means salts of compounds of thepresent invention which are pharmaceutically acceptable, as definedabove, and which possess the desired pharmacological activity. Suchsalts include acid addition salts formed with inorganic acids such ashydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid, and the like; or with organic acids such as aceticacid, propionic acid, hexanoic acid, heptanoic acid,cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid,malonic acid, succinic acid, malic acid, maleic acid, fumaric acid,tartaric acid, citric acid, benzoic acid, o-(4-hydroxybenzoyl)benzoicacid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonicacid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid,benzenesulfonic acid, p-chlorobenzenesulfonic acid,2-naphthalenesulfonic acid, p-toluenesulfonic acid, camphorsulfonicacid, 4-methylbicyclo[2.2.2]oct-2-ene-1-carboxylic acid, glucoheptonicacid, 4,4′-methylenebis(3-hydroxy-2-ene-1-carboxylic acid),3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid,lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoicacid, salicylic acid, stearic acid, muconic acid and the like.

Pharmaceutically acceptable salts also include base addition salts whichmay be formed when acidic protons present are capable of reacting withinorganic or organic bases. Acceptable inorganic bases include sodiumhydroxide, sodium carbonate, potassium hydroxide, aluminum hydroxide andcalcium hydroxide. Acceptable organic bases include ethanolamine,diethanolamine, triethanolamine, tromethamine, N-methylglucamine and thelike.

“Prodrug” means a compound that is convertible in vivo metabolicallyinto an inhibitor according to the present invention. The prodrug itselfmay or may not also have HDAC inhibitory activity. For example, aninhibitor comprising a hydroxy group may be administered as an esterthat is converted by hydrolysis in vivo to the hydroxy compound.Suitable esters that may be converted in vivo into hydroxy compoundsinclude acetates, citrates, lactates, tartrates, malonates, oxalates,salicylates, propionates, succinates, fumarates, maleates,methylene-bis-b-hydroxynaphthoates, gentisates, isethionates,di-p-toluoyltartrates, methanesulfonates, ethanesulfonates,benzenesulfonates, p-toluenesulfonates, cyclohexylsulfamates, quinates,esters of amino acids, and the like. Similarly, an inhibitor comprisingan amine group may be administered as an amide that is converted byhydrolysis in vivo to the amine compound.

“Protected derivatives” means derivatives of inhibitors in which areactive site or sites are blocked with protecting groups. Protectedderivatives are useful in the preparation of inhibitors or in themselvesmay be active as inhibitors. A comprehensive list of suitable protectinggroups can be found in T. W. Greene, Protecting Groups in OrganicSynthesis, 3rd edition, John Wiley & Sons, Inc. 1999.

“Ring” means a carbocyclic or a heterocyclic system.

“Substituted or unsubstituted” means that a given moiety may consist ofonly hydrogen substituents through available valencies (unsubstituted)or may further comprise one or more non-hydrogen substituents throughavailable valencies (substituted) that are not otherwise specified bythe name of the given moiety. For example, isopropyl is an example of anethylene moiety that is substituted by —CH₃. In general, a non-hydrogensubstituent may be any substituent that may be bound to an atom of thegiven moiety that is specified to be substituted. Examples ofsubstituents include, but are not limited to, aldehyde, alicyclic,aliphatic, (C₁₋₁₀)alkyl, alkylene, alkylidene, amide, amino, aminoalkyl,aromatic, aryl, bicycloalkyl, bicycloaryl, carbamoyl, carbocyclyl,carboxyl, carbonyl group, cycloalkyl, cycloalkylene, ester, halo,heterobicycloalkyl, heterocycloalkylene, heteroaryl, heterobicycloaryl,heterocycloalkyl, oxo, hydroxy, iminoketone, ketone, nitro, oxaalkyl,and oxoalkyl moieties, each of which may optionally also be substitutedor unsubstituted.

“Sulfinyl” means the radical —SO—. It is noted that the sulfinyl radicalmay be further substituted with a variety of substituents to formdifferent sulfinyl groups including sulfinic acids, sulfinamides,sulfinyl esters, and sulfoxides.

“Sulfonyl” means the radical —SO₂—. It is noted that the sulfonylradical may be further substituted with a variety of substituents toform different sulfonyl groups including sulfonic acids, sulfonamides,sulfonate esters, and sulfones.

“Therapeutically effective amount” means that amount which, whenadministered to an animal for treating a disease, is sufficient toeffect such treatment for the disease.

“Thiocarbonyl” means the radical —CS—. It is noted that the thiocarbonylradical may be further substituted with a variety of substituents toform different thiocarbonyl groups including thioacids, thioamides,thioesters, and thioketones.

“Treatment” or “treating” means any administration of a compound of thepresent invention and includes:

(1) preventing the disease from occurring in an animal which may bepredisposed to the disease but does not yet experience or display thepathology or symptomatology of the disease,

(2) inhibiting the disease in an animal that is experiencing ordisplaying the pathology or symptomatology of the diseased (i.e.,arresting further development of the pathology and/or symptomatology),or

(3) ameliorating the disease in an animal that is experiencing ordisplaying the pathology or symptomatology of the diseased (i.e.,reversing the pathology and/or symptomatology).

It is noted in regard to all of the definitions provided herein that thedefinitions should be interpreted as being open ended in the sense thatfurther substituents beyond those specified may be included. Hence, a C₁alkyl indicates that there is one carbon atom but does not indicate whatare the substituents on the carbon atom. Hence, a C₁ alkyl comprisesmethyl (i.e., —CH₃) as well as —CR_(a)R_(b)R_(c) where R_(a), R_(b), andR_(c) may each independently be hydrogen or any other substituent wherethe atom attached to the carbon is a heteroatom or cyano. Hence, CF₃,CH₂OH and CH₂CN, for example, are all C₁ alkyls.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to compounds, compositions, kits andarticles of manufacture that may be used to inhibit histone deacetylases(HDACs) and, in particular, Class I HDACs such as HDAC1, HDAC2, HDAC6and HDAC8.

At least seventeen human genes that encode proven or putative HDACs havebeen identified to date, some of which are described in Johnstone, R.W., “Histone-Deacetylase Inhibitors: Novel Drugs for the Treatment ofCancer”, Nature Reviews, Volume I, pp. 287-299, (2002) and PCTPublication Nos. 00/10583, 01/18045, 01/42437 and 02/08273.

HDACs have been categorized into three distinct classes based on theirrelative size and sequence homology. The different HDACs (Homo sapiens),HDAC classes, sequences and references describing the different HDACsare provided in Tables 1-3. TABLE 1 CLASS I HDACs GenBank HDAC AccessionNumber Reference 1 NP_004955 Histone deacetylase: a regulator oftranscription, Wolffe, A. P., Science 272 (5260), 371-372 (1996) 2NP_001518 Isolation and mapping of a human gene (RPD3L1) that ishomologous to RPD3, a transcription factor in Saccharomyces cerevisiae;Furukawa, Y., Kawakami, T., Sudo, K., Inazawa, J., Matsumine, A.,Akiyama, T. and Nakamura, Y., Cytogenet. Cell Genet. 73 (1-2), 130-133(1996) 3 NP_003874 Isolation and characterization of cDNAs correspondingto an additional member of the human histone deacetylase gene family,Yang, W. M., Yao, Y. L., Sun, J. M., Davie, J. R. and Seto, E., J. Biol.Chem. 272 (44), 28001-28007 (1997) 8 NP_060956 Buggy, J. J., Sideris, M.L., Mak, P., Lorimer, D. D., McIntosh, B. and Clark, J. M. Biochem. J.350 Pt 1, 199-205 (2000) 11 NP_079103 Cloning and FunctionalCharacterization of HDAC11, a Novel Member of the Human HistoneDeacetylase Family, Gao, L., Cueto, M. A., Asselbergs, F. and Atadja,P., J. Biol. Chem. 277 (28), 25748-25755 (2002)

TABLE 2 CLASS II HDACs GenBank HDAC Accession Number Reference 4NP_006028 Transcriptional control. Sinful repression, Wolffe, A. P.,Nature 387 (6628), 16-17 (1997) 5 NP_631944 Prediction of the codingsequences of unidentified human genes. IX. The complete sequences of 100new cDNA clones from brain which can code for large proteins in vitro,Nagase, T., Ishikawa, K., Miyajima, N., Tanaka, A., Kotani, H., Nomura,N. and Ohara, O., DNA Res. 5 (1), 31-39 (1998) 6 NP_006035Transcriptional control. Sinful repression, Wolffe, A. P., Nature 387(6628), 16-17 (1997) 7 NP_057680 Isolation of a novel histonedeacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression, Kao, H. Y., Downes, M., Ordentlich, P. and Evans,R. M., Genes Dev. 14 (1), 55-66 (2000) 9 NP_478056 MEF-2 function ismodified by a novel co-repressor, MITR, Sparrow, D. B., Miska, E. A.,Langley, E., Reynaud-Deonauth, S., Kotecha, S., Towers, N., Spohr, G.,Kouzarides, T. and Mohun, T. J., EMBO J. 18 (18), 5085-5098 (1999) 10NP_114408 Isolation and characterization of mammalian HDAC10, a novelhistone deacetylase, Kao, H. Y., Lee, C. H., Komarov, A., Han, C. C. andEvans, R. M., J. Biol. Chem. 277 (1), 187-193 (2002)

TABLE 3 CLASS III HDACs GenBank HDAC Accession Number Reference Sirtuin1 NP_036370 Characterization of five human cDNAs with homology to theyeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and mayhave protein ADP- ribosyltransferase activity; Frye, R. A.; Biochem.Biophys. Res. Commun. 260 (1), 273-279 (1999) Sirtuin 2 NP_085096/ A‘double adaptor’ method for improved shotgun NP_036369 libraryconstruction; Andersson, B., Wentland, M. A., Ricafrente, J. Y., Liu, W.and Gibbs, R. A.; Anal. Biochem. 236 (1), 107-113 (1996) Sirtuin 3NP_036371 Characterization of five human cDNAs with homology to theyeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and mayhave protein ADP- ribosyltransferase activity; Frye, R. A.; Biochem.Biophys. Res. Commun. 260 (1), 273-279 (1999) Sirtuin 4 NP_036372Characterization of five human cDNAs with homology to the yeast SIR2gene: Sir2-like proteins (sirtuins) metabolize NAD and may have proteinADP- ribosyltransferase activity; Frye, R. A.; Biochem. Biophys. Res.Commun. 260 (1), 273-279 (1999) Sirtuin 5 NP_112534/ Characterization offive human cDNAs with homology NP_036373 to the yeast SIR2 gene:Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity; Frye, R. A.; Biochem. Biophys. Res. Commun.260 (1), 273-279 (1999) Sirtuin 6 NP_057623 Phylogenetic classificationof prokaryotic and eukaryotic Sir2-like proteins; Frye, R. A.; Biochem.Biophys. Res. Commun. 273 (2), 793-798 (2000) Sirtuin 7 NP_057622Phylogenetic classification of prokaryotic and eukaryotic Sir2-likeproteins; Frye, R. A.; Biochem. Biophys. Res. Commun. 273 (2), 793-798(2000)

Of particular note are Class I HDACs. All Class I HDACs appear to besensitive to inhibition by trichostatin A (TSA). Of particular noteHDAC2 and HDAC8, proteins whose crystal structures Applicants determinedand used in conjunction with arriving at the present invention.

HDAC2 is a 488 residue, 55 kDa protein localized to the nucleus of awide array of tissues, as well as several human tumor cell lines. Thewild-type form of full length HDAC2 is described in GenBank AccessionNumber NM 001527, Furukawa, Y. et al., Cryogenet. Cell Genet., 73 (1-2),130-133 (1996). Zn²⁺ is likely native to the protein and required forHDAC2 activity.

HDAC8 is a 377 residue, 42 kDa protein localized to the nucleus of awide array of tissues, as well as several human tumor cell lines. Thewild-type form of full length HDAC8 is described in GenBank AccessionNumber NP 060956; Buggy, J. J. et al., Biochem. J., 350 (Pt 1), 199-205(2000). Zn²⁺ is likely native to the protein and required for HDAC8activity.

It is noted that the compounds of the present invention may also possessinhibitory activity for other HDAC family members and thus may be usedto address disease states associated with these other family members.

Crystal Structure of Histone Deacetylase

Syrrx, Inc. (now Takeda San Diego, Inc.) in San Diego, Calif. solved thecrystal structure for HDAC2. HDAC2 was found to adopt an open-faced α/βstructure consisting of 8 central parallel β-sheets sandwiched between12 α-helices. The ligand binding cleft lies almost in the plane of thecentral β-sheet, and is formed primarily by loops emanating from thecarboxy-terminal ends of the β-strands comprising the sheet. Residueswhich form loop regions extending between β-strand 1 and α-helix 1 andbetween α-helix 4 and α-helix 5, provide key surface interactions withbound ligands. Residues which form loop regions extending betweenβ-strand 3 and α-helix 6 and between β-strand 4 and α-helix 7 andbetween β-strand 8 and α-helix 10 play important roles in defining theshape of the ligand binding pocket, and are involved in a number of keyinteractions with the bound ligands.

HDAC8 was found to have a single domain structure belonging to the openα/β class of folds. The structure consists of a central 8-strandedparallel β-sheet sandwiched between layers of α-helices. The ligandbinding clefts lie almost in the plane of the central β-sheet, and areformed primarily by loops emanating from the carboxy-terminal ends ofthe β-strands comprising the sheet. There are two large structuralextensions, which occur beyond the core of the α/β motif, off the secondand last β-strands of the central β-sheet. Residues contained in theextension off the second β-strand form a globular “cap” over the core ofthe protein, play an important role in defining the shape of the ligandbinding pockets, and are involved in a number of key interactions withthe bound ligands.

Knowledge of the crystal structures was used to guide the design of theHDAC inhibitors provided herein.

HDAC Inhibitors

In one embodiment, HDAC inhibitors of the present invention comprise:

wherein:

n is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomto which L is attached;

J₁ is selected from the group consisting of —CR₇R₇′—and —NR₁₀—;

J₂ is selected from the group consisting of —CR₂₀R₂₀′ and —NR₁₀—;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ are taken together to form asubstituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₅, R₅′, R₆, R₆′, R₇, and R₇′, R₂₀ and R₂₀′ are each independentlyselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇, R₇′,R₂₀ and R₂₀′ may be taken together to form a substituted orunsubstituted ring, provided that R₅, R₆, R₇ and R₂₀, are eachindependently absent when the C to which they are bound is bound to L,and R₅′, R₆′, R₇′ and R₂₀′, are each independently absent when the C towhich they are bound form part of a double bond; and

R₈, R₁₀ and R₁₉ are each individually selected from the group consistingof hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′, R₂₀, R₂₀′, R₁₀ and R₁₉ may be taken together to form a substitutedor unsubstituted ring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′, R₇, R₇′,R₂₀, R₂₀′ and R₁₉ may be taken together to form a substituted orunsubstituted ring, or R₁₉ and any one of R₅, R₅′, R₆, R₆′, R₂₀ andR₂₀′, may be taken together to form a substituted or unsubstituted ring,provided that R₈, R₁₀ and R₁₉ are each independently absent when the Nto which they are bound is bound to L, and R₈, R₁₀ and R₁₉ are eachindependently absent when the N to which they are bound form part of adouble bond.

In another embodiment, HDAC inhibitors of the present inventioncomprise:

wherein:

n is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₅, R₅′, R₆, R₆′, R₇ and R₇′ are each independently selected from thegroup consisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,amido, carboxamido, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇ and R₇′may be taken together to form a substituted or unsubstituted ring,provided that R₅, R₆ and R₇ are each independently absent when the C towhich they are bound is bound to L, and R₅′, R₆′ and R₇′ are eachindependently absent when the C to which they are bound form part of adouble bond; and

R₈ and R₁₀ are each individually selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′ and R₁₀ may be taken together to form a substituted or unsubstitutedring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′, R₇ and R₇′ may be takentogether to form a substituted or unsubstituted ring, provided that R₈and R₁₀ are each independently absent when the N to which they are boundis bound to L, and R₈ and R₁₀ are absent when the N to which they arebound form part of a double bond.

In another embodiment, HDAC inhibitors of the present invention comprisea compound selected from the group consisting of:

wherein:

n is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₅, R₅′, R₆, R₆′, R₇ and R₇′ are each independently selected from thegroup consisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,amido, carboxamido, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇ and R₇′may be taken together to form a substituted or unsubstituted ring,provided that R₅′, R₆′ and R₇′ are each independently absent when the Cto which they are bound form part of a double bond; and

R₈ and R₁₀ are each individually selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′ and R₁₀ may be taken together to form a substituted or unsubstitutedring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′, R₇ and R₇′ may be takentogether to form a substituted or unsubstituted ring, provided that R₉and R₁₀ are each independently absent when the N to which they are boundform part of a double bond.

In yet another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

n is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₅, R₅′, R₆, R₆′, R₇ and R₇′ are each independently selected from thegroup consisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,amido, carboxamido, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇ and R₇′may be taken together to form a substituted or unsubstituted ring,provided that R₅′, R₆′ and R₇′ are each independently absent when the Cto which they are bound form part of a double bond;

R₈ and R₁₀ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′ and R₁₀ may be taken together to form a substituted or unsubstitutedring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′, R₇ and R₇′ may be takentogether to form a substituted or unsubstituted ring, provided that R₈and R₁₀ are each independently absent when the N to which they are boundform part of a double bond; and

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted.

In still another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₅, R₅′, R₆, R₆′, R₇ and R₇′ are each independently selected from thegroup consisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,amido, carboxamido, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇ and R₇′may be taken together to form a substituted or unsubstituted ring,provided that R₅′, R₆′ and R₇′ are each independently absent when the Cto which they are bound form part of a double bond;

R₈ and R₁₀ are independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′ and R₁₀ may be taken together to form a substituted or unsubstitutedring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′, R₇ and R₇′ may be takentogether to form a substituted or unsubstituted ring, provided that R₈and R₁₀ are absent when the N to which they are bound form part of adouble bond; and each R₉ is independently selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₋)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and any one of R₃,R₅, R₅′, R₇, R₇′, R₈ and R₁₀ may be taken together to form a substitutedor unsubstituted ring.

In a further embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₅, R₅′, R₆, R₆′, R₇ and R₇′ are each independently selected from thegroup consisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,amido, carboxamido, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇ and R₇′may be taken together to form a substituted or unsubstituted ring,provided that R₅′, R₆′ and R₇′ are each independently absent when the Cto which they are bound form part of a double bond;

R₈ and R₁₀ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′ and R₁₀ may be taken together to form a substituted or unsubstitutedring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′, R₇ and R₇′ may be takentogether to form a substituted or unsubstituted ring, provided that R₈or R₁₀ are each independently absent when the N to which it is boundform part of a double bond;

each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and any one of R₃,R₅, R₅′, R₇, R₇′, R₈ and R₁₀ may be taken together to form a substitutedor unsubstituted ring; and

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring.

In still a further embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₅, R₅′, R₆, R₆′, R₇ and R₇′ are each independently selected from thegroup consisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,amido, carboxamido, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇ and R₇′may be taken together to form a substituted or unsubstituted ring,provided that R₅′, R₆′ and R₇′ are each independently absent when the Cto which they are bound form part of a double bond;

R₈ and R₁₀ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′ and R₁₀ may be taken together to form a substituted or unsubstitutedring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′, R₇ and R₇′ may be takentogether to form a substituted or unsubstituted ring, provided that R₈is absent when the N to which it is bound forms part of a double bond;

each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and any one of R₅,R₅′, R₇, R₇′, R₈ and R₁₀ may be taken together to form a substituted orunsubstituted ring; and

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring.

In yet a further embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

n is selected from the group consisting of 0, 1, 2, 3 and 4;

p is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀lo)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₇ may be taken together toform a substituted or unsubstituted ring; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.

In another embodiment, HDAC inhibitors of the present invention comprisea compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

p is selected from the group consisting of 0, 1, 2, 3 and 4;

L is a linker providing a 0-6 atom separation between the two ringsatoms to which L is attached;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and R₃ may betaken together to form a substituted or unsubstituted ring; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ may be taken together toform a substituted or unsubstituted ring.

In still another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

p is selected from the group consisting of 0, 1, 2, 3 and 4

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₀₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and R₃ may betaken together to form a substituted or unsubstituted ring;

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.

In yet another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

p is selected from the group consisting of 0, 1, 2, 3 and 4

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ may be taken together toform a substituted or unsubstituted ring;

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₇ or R₉ may be taken togetherto form a substituted or unsubstituted ring; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.

In one variation of each of the above embodiments, m is 0, R₁₁ ishydrogen, and R₁₂ is selected from the group consisting of hydroxy,alkoxy, halo, amido, carboxamido, and (C₁₋₁₀)alkylamido, eachsubstituted or unsubstituted.

In yet another variation, n is 0, p is 2, and R₁₂ is selected from thegroup consisting of hydroxy, alkoxy, and halo.

In still another variation, R₇ is hydrogen, and R₁₂ is alkoxy.

In still another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

n is selected from the group consisting of 0, 1, 2, 3 and 4;

PATENT

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₅, R₅′, R₆ and R₆′ are each independently selected from the groupconsisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido,carboxamido, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, and R₆′ may betaken together to form a substituted or unsubstituted ring, providedthat R₅′ and R₆′ are each independently absent when the C to which theyare bound form part of a double bond; and

R₈, R₁₀ and R₁₉, are each individually selected from the groupconsisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₁₀and R₁₉ may be taken together to form a substituted or unsubstitutedring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′ and R₁₉ may be takentogether to form a substituted or unsubstituted ring, or R₁₉ and any oneof R₅, R₅′, R₆ and R₆′ may be taken together to form a substituted orunsubstituted ring, provided that R₈, R₁₀ and R₁₉ are each independentlyabsent when the N to which they are bound forms part of a double bond.

In still another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₅, R₅′, R₆ and R₆′ are each independently selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido,carboxamido, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆ and R₆′ may betaken together to form a substituted or unsubstituted ring, providedthat R₅′ and R₆′ are each independently absent when the C to which theyare bound form part of a double bond;

R₈, R₁₀ and R₁₉ are each independently selected from the groupconsisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₁₀and R₁₉ may be taken together to form a substituted or unsubstitutedring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′ and R₁₉ may be takentogether to form a substituted or unsubstituted ring, or R₁₉ and any oneof R₅, R₅′, R₆ and R₆′ may be taken together to form a substituted orunsubstituted ring, provided that R₈, R₁₀ and R₁₉ are each independentlyabsent when the N to which they are bound forms part of a double bond.

each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and any one of R₃,R₅, R₅′, R₈, R₁₀ and R₁₉ may be taken together to form a substituted orunsubstituted ring; and

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring.

In still another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

p is selected from the group consisting of 0, 1, 2, 3 and 4;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and R₃ may betaken together to form a substituted or unsubstituted ring;

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₁₁ may be taken together toform a substituted or unsubstituted.

In still another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

p is selected from the group consisting of 0, 1, 2, 3 and 4;

R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ may be taken together toform a substituted or unsubstituted ring;

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamide, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₁₁ may be taken together toform a substituted or unsubstituted ring.

In still another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

n is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₅, R₅′, R₆, R₆′, R₇, R₇′, R₂₀ and R₂₀′ are each independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, oxo, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇, R₇′,R₂₀ and R₂₀′may be taken together to form a substituted or unsubstitutedring, provided that R₅′, R₆′, R₇′ and R₂₀′, are each independentlyabsent when the C to which they are bound form part of a double bond;and

R₈ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′, R₂₀ and R₂₀′ may be taken together to form a substituted orunsubstituted ring, provided that R₈ is absent when the N to which it isbound forms part of a double bond.

In still another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₅, R₅′, R₆, R₆′, R₇, R₇′, R₂₀ and R₂₀′ are each independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, oxo, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇, R₇′,R₂₀ and R₂₀′ may be taken together to form a substituted orunsubstituted ring, provided that R₅′, R₆′, R₇′ and R₂₀′, are eachindependently absent when the C to which they are bound form part of adouble bond; and

R₈ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′, R₂₀ and R₂₀′ may be taken together to form a substituted orunsubstituted ring, provided that R₈ is absent when the N to which it isbound forms part of a double bond;

each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and any one of R₃,R₅, R₅′, R₆, R₆′, R₇, R₇′, R₂₀, R₂₀′ and R₈ may be taken together toform a substituted or unsubstituted ring; and

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring.

In still another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

p is selected from the group consisting of 0, 1, 2, 3 and 4;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and R₃ may betaken together to form a substituted or unsubstituted ring;

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₁₁ may be taken together toform a substituted or unsubstituted ring.

In still another embodiment, HDAC inhibitors of the present inventioncomprise a compound selected from the group consisting of:

wherein:

m is selected from the group consisting of 0, 1, 2, 3 and 4;

n is selected from the group consisting of 0, 1, 2, 3 and 4;

p is selected from the group consisting of 0, 1, 2, 3 and 4;

R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ may be taken together toform a substituted or unsubstituted ring;

R₁₁ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₁₁ may be taken together toform a substituted or unsubstituted ring.

In one variation of each of the above embodiments, R₁ and R₂ are eachindependently selected from the group consisting of hydrogen, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl and imino(C₁₋₃)alkyl, eachsubstituted or unsubstituted.

In another variation of each of the above embodiments and variations, R₁is hydrogen or a substituent convertible in vivo to hydrogen. In stillanother variation of each of the above embodiments and variations, R₂ ishydrogen or a substituent convertible in vivo to hydrogen. In yetanother variation of each of the above embodiments and variations, R₃ ishydrogen or a substituent convertible in vivo to hydrogen.

In a further variation of each of the above embodiments and variations,R₄ is selected from the group consisting of hydrogen, halo, aryl andheteroaryl, each substituted or unsubstituted. In yet a furthervariation of each of the above embodiments and variations, R₄ isselected from the group consisting of phenyl, oxazolyl, thiazolyl,morpholinyl and thiomorpholinyl, each substituted or unsubstituted.

In still a further variation of each of the above embodiments andvariations, R₅, R₆, R₇ and R₂₀ are independently selected from the groupconsisting of carbonyl, oxo, amino, (C₁₋₁₀)alkylamino, amido,carboxamido, cyano, alkoxy, (C₁₋₁₀)alkyl, aryl, and heteroaryl, eachsubstituted or unsubstituted.

In another variation of each of the above embodiments and variations, R₅and R₆ are taken together to form a substituted or unsubstituted ring.In one variation, the ring is an aryl or heteroaryl, each substituted orunsubstituted. In another variation, the ring is substituted with asubstituent selected from the group consisting of halo, alkoxy,amino(C₁₋₁₀)alkoxy, amino(C₁₋₁₀)alkylamino, amino(C₁₋₁₀)alkylsulfanyl,halo(C₁₋₁₀ )alkyl, aryl and heteroaryl, each substituted orunsubstituted. In yet another variation, the ring is substituted with asubstituent selected from the group consisting of thiopheneyl,pyridinyl, furanyl and pyrimidinyl, each substituted or unsubstituted.

In still another variation, the ring is substituted with—O—CH₂CH₂—NR₁₃R₁₄. In a further variation, the ring is substituted with—NH—CH₂CH₂—NR₁₃R₁₄. In yet a further variation, the ring is substitutedwith —S—CH₂CH₂—NR₁₃R₁₄. In each of these variations, R₁₃ and R₁₄ areeach independently selected from the group consisting of hydrogen,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl, hetero(C₈₋₁₂)bicycloaryl (C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₃ and R₁₄ may be taken together toform a substituted or unsubstituted ring. In other embodiments, R₁₃ andR₁₄ are each independently selected from the group consisting ofhydrogen, (C₁₋₁₀)alkyl, (C₃₋₁₂)cycloalkyl, and heteroaryl, eachsubstituted or unsubstituted. In still other embodiments, R₁₃ and R₁₄are taken together to form a ring selected from the group consisting ofmorpholinyl, pyrrolidinyl, piperazinyl and thiomorpholinyl, eachsubstituted or unsubstituted.

In another variation of each of the above embodiments and variations,R₈, R₁₀ and R₁₉ are selected from the group consisting of hydrogen andsubstituted or unsubstituted (C₁₋₁₀)alkyl.

In still another variation of each of the above embodiments andvariations, L is a linker providing a 1-5 atom separation between thetwo ring atoms to which L is attached. In yet another variation of eachof the above embodiments and variations, L is a linker providing a 1-3atom separation between the two ring atoms to which L is attached. In afurther variation of each of the above embodiments and variations, L isa substituted or unsubstituted alkylene. In yet a further variation ofeach of the above embodiments and variations, wherein L is —CH₂—. Inanother variation of each of the above embodiments and variations, L isselected from the group consisting of —NR₁₅—; —NR₁₅—CH₂—; —O—CH₂—;—S—CH₂—; —CH₂—NR₁₅—; —CH₂—O— and —CH₂—S—, wherein R₁₅ is selected fromthe group consisting of hydrogen, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted.

In still another variation of each of the above embodiments andvariations, A₁ is selected from the group consisting of aryl andheteroaryl, each substituted or unsubstituted. In yet another variationof each of the above embodiments and variations, A₁ is a substituted orunsubstituted phenylene. In a further variation of each of the aboveembodiments and variations, A₁ is a substituted or unsubstituted1,4-phenylene. In still a further variation of each of the aboveembodiments and variations, A₁ is selected from the group consisting ofa thiophenediyl, furandiyl, pyrrolediyl, thiazolediyl, oxazolediyl,imidazolediyl and pyridinediyl, each substituted or unsubstituted.

In another variation of each of the above embodiments and variations, A₁comprises:

wherein:

each X is independently selected from the group consisting of CR₁₆ andN; and

each R₁₆ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₆ is absent when the C to which it isbound is further bound to L or the carbonyl adjacent to A₁.

Particular examples of compounds according to the present inventioninclude, but are not limited to:

-   -   4-((1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((5-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((5-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;    -   N-(2-aminophenyl)-4-((5-nitro-1H-indazol-1-yl)methyl)benzamide;    -   4-((5-benzamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((5-amino-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   N-(2-aminophenyl)-4-((5-nitro-2H-indazol-2-yl)methyl)benzamide;    -   4-((5-amino-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((5-benzamido-2H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   2-Methoxyethyl        2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate;    -   Methyl        2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate;    -   2-Methoxyethyl        1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;    -   Methyl        1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;    -   Benzyl        1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;    -   Benzyl        2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate;    -   N-(4-Amino-biphenyl-3-yl)-4-(5-nitro-indazol-2-ylmethyl)-benzamide;    -   N-(2-(4-((2-Aminophenyl)carbamoyl)benzyl)-2H-indazol-5-yl)morpholine-4-carboxamide;    -   5-((2H-Indazol-2-yl)methyl)-N-(2-aminophenyl)thiophene-2-carboxamide;    -   N-(2-Aminophenyl)-5-((5-nitro-2H-indazol-2-yl)methyl)thiophene-2-carboxamide;    -   N-(1-(4-((2-Aminophenyl)carbamoyl)benzyl)-1H-indazol-5-yl)morpholine-4-carboxamide;    -   2-Morpholinoethyl        1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;    -   Pyridin-3-ylmethyl        1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;    -   5-((1H-Indazol-1-yl)methyl)-N-(2-aminophenyl)thiophene-2-carboxamide;    -   4-((2H-Pyrazolo[3,4-b]pyridin-2-yl)methyl)-N-(2-aminophenyl)benzamide;    -   N-(4-Amino-biphenyl-3-yl)-4-pyrazolo        [3,4-b]pyridin-2-ylmethyl-benzamide;    -   N-(4-Amino-biphenyl-3-yl)-4-indazol-2-ylmethyl-benzamide;    -   N-(2-Aminophenyl)-4-((3-methyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-Aminophenyl)-4-((3-methyl-2H-indazol-2-yl)methyl)benzamide;    -   4-((1H-indazol-3-ylamino)methyl)-N-(2-aminophenyl)benzamide;    -   4-((1H-pyrazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   N-(2-(4-((2-Aminophenyl)carbamoyl)benzyl)-2H-indazol-5-yl)morpholine-4-carboxamide;    -   Methyl 3-(4-((2H-indazol-2-yl)methyl)benzamido)-4-aminobenzoate;    -   N-(2-aminophenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((6-fluoro-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((6-fluoro-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-fluoro-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-fluoro-2H-indazol-2-yl)methyl)benzamide;    -   4-(1-(1H-indazol-1-yl)propan-2-yl)-N-(2-aminophenyl)benzamide;    -   4-(2-(1H-indazol-1-yl)ethyl)-N-(2-aminophenyl)benzamide;    -   4-(2-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide;    -   N-(2-aminophenyl)-4-((4-chloro-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4-chloro-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4,6-difluoro-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4,6-difluoro-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((7-fluoro-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((7-fluoro-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4-fluoro-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4-fluoro-2H-indazol-2-yl)methyl)benzamide;    -   (R)-4-(1-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide;    -   (S)-4-(1-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide;    -   N-(2-aminophenyl)-4-((7-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((7-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5,6-difluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5,6-difluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((6-methoxy-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((6-methoxy-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-chloro-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-chloro-2H-indazol-2-yl)methyl)benzamide;    -   4-((3-amino-5-(trifluoromethyl)-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((3-amino-5-(trifluoromethyl)-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   N-(2-aminophenyl)-4-((3-oxo-2,3-dihydro-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-oxo-1H-indazol-2(3H)-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((6-methoxy-3-methyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((6-methoxy-3-methyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((6-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((6-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-ethyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-ethyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((6-hydroxy-3-methyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((6-hydroxy-3-methyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-phenyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-phenyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-methoxy-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-methoxy-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3,5-dimethyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3,5-dimethyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((7-methoxy-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4-methoxy-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((7-methoxy-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4-methoxy-1H-indazol-1-yl)methyl)benzamide;    -   4-((6-acetamido-3-methyl-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((6-acetamido-3-methyl-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((3-amino-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((6-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((6-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;    -   N-(2-aminophenyl)-4-((3-methyl-7-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-methyl-6-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-methyl-6-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-methyl-5-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-methyl-5-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;    -   4-((3-amino-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   N-(2-aminophenyl)-4-((5-hydroxy-6-methoxy-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5,6-dimethoxy-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5,6-dimethoxy-1H-indazol-1-yl)methyl)benzamide;    -   4-((1H-benzo[d][1,2,3]triazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((2H-benzo[d][1,2,3]triazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((5-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-(piperazin-1-yl)ethyl)-1H-pyrazole-4-carboxamide;    -   4-((2H-indazol-2-yl)methyl)-N-(4-aminopyrimidin-5-yl)benzamide;    -   4-((5-acetamido-3-amino-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((5-acetamido-3-methyl-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((5-acetamido-3-methyl-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-(1-(1H-indazol-1-yl)ethyl)-N-(2-aminophenyl)benzamide;    -   4-(1-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide;    -   5-((5-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)thiophene-2-carboxamide;    -   4-((2H-indazol-2-yl)methyl)-N-(2-amino-5-(thiophen-2-yl)phenyl)benzamide;    -   N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4,6-difluoro-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4,6-difluoro-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((6-methoxy-3-methyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((6-methoxy-3-methyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((6-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-1H-pyrazole-4-carboxylic        acid;    -   N-(2-aminophenyl)-4-((3-methyl-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3,5        -dimethyl-1H-pyrazol-1-yl)methyl)benzamide;    -   Ethyl        1-(4-(2-aminophenylcarbamoyl)benzyl)-1H-pyrazole-4-carboxylate;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridin-2-ylmethyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-phenyl-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-benzyl-1H-pyrazole-4-carboxamide;    -   N-(2-aminophenyl)-4-((4,5,6,7-tetrahydro-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4,5,6,7-tetrahydro-1H-indazol-1-yl)methyl)benzamide;    -   4-((1H-pyrazol-3-ylamino)methyl)-N-(2-aminophenyl)benzamide;    -   4-((5-amino-1H-pyrazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((3-amino-1H-pyrazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-methyl-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-ethyl-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N,N-dimethyl-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-isopropyl-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-cyclopropyl-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(cyclopropylmethyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-(dimethylamino)ethyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-hydroxyethyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-(dimethylamino)propyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridin-3-ylmethyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridin-4-ylmethyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-morpholinoethyl)-1H-pyrazole-4-carboxamide;    -   N-(2-aminophenyl)-4-((5-methyl-1H-pyrazol-1-yl)methyl)benzamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-propyl-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-isobutyl-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-methoxyethyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-methoxypropyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-hydroxypropyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-morpholinopropyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-(piperidin-1-yl)ethyl)-1H-pyrazole-4-carboxamide;    -   1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-(4-methylpiperazin-1-yl)propyl)-1H-pyrazole-4-carboxamide;    -   4-((1H-Pyrrolo[2,3-b]pyridin-1-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((1H-Indol-3-yl)methyl)-N-(2-aminophenyl)benzamide;    -   4-((1H-indazol-1-yl)methyl)-N-(2-amino-5-fluorophenyl)benzamide;    -   4-((2H-indazol-2-yl)methyl)-N-(2-amino-5-fluorophenyl)benzamide;    -   4-((1H-indazol-1-yl)methyl)-N-(2-amino-5-fluorophenyl)-3-methylbenzamide;    -   4-((2H-indazol-2-yl)methyl)-N-(2-amino-5-fluorophenyl)-3-methylbenzamide;    -   N-(2-aminophenyl)-3-methyl-4-((3-methyl-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-3-methyl-4-((3-methyl-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-cyano-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-cyano-2H-indazol-2-yl)methyl)benzamide;    -   1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazole-3-carboxylic        acid;    -   2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazole-3-carboxylic        acid;    -   N-(2-aminophenyl)-4-((5-cyano-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-cyano-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-(pyridin-2-yl)-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-(pyridin-2-yl)-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-(dimethylamino)-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-(dimethylamino)-2H-indazol-2-yl)methyl)benzamide;    -   4-((1H-indazol-1-yl)methyl)-N-(2-amino-5-(furan-2-yl)phenyl)benzamide;    -   4-((2H-indazol-2-yl)methyl)-N-(2-amino-5-(furan-2-yl)phenyl)benzamide;    -   N-(2-aminophenyl)-4-((3-methoxy-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-methoxy-2H-indazol-2-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-(methoxymethylamino)-1H-indazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-(methoxymethylamino)-2H-indazol-2-yl)methyl)benzamide;    -   4-((1H-pyrazol-1-yl)methyl)-N-(2-amino-5-fluorophenyl)benzamide;    -   N-(2-amino-5-fluorophenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide;    -   4-((1H-pyrazol-1-yl)methyl)-N-(2-aminophenyl)-3-methylbenzamide;    -   N-(2-amino-5-fluorophenyl)-3-methyl-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4-(furan-2-yl)-1H-pyrazol-1-yl)methyl)benzamide;    -   1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-pyrazole-4-carboxylic        acid;    -   N-(2-aminophenyl)-4-((3-ethyl-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-ethyl-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((4-phenyl-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-3-methyl-4-((5-methyl-4-phenyl-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-cyano-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-(pyridin-2-yl)-1H-pyrazol-1-yl)methyl)benzamide;    -   4-((1H-pyrazol-1-yl)methyl)-N-(2-amino-5-(furan-2-yl)phenyl)benzamide;    -   N-(2-amino-5-(furan-2-yl)phenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide;    -   (S)-4-(1-(1H-pyrazol-1-yl)ethyl)-N-(2-aminophenyl)benzamide;    -   (R)-4-(1-(1H-pyrazol-1-yl)ethyl)-N-(2-aminophenyl)benzamide;    -   N-(2-aminophenyl)-4-((3-(pyridin-2-yl)-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-methoxy-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((3-(methoxymethylamino)-1H-pyrazol-1-yl)methyl)benzamide;    -   N-(2-aminophenyl)-4-((5-(methoxymethylamino)-1H-pyrazol-1-yl)methyl)benzamide;        and    -   N-(2-aminophenyl)-4-((3-methoxy-1H-pyrazol-1-yl)methyl)benzamide.

It is noted that the compounds of the present invention may be in theform of a pharmaceutically acceptable salt, biohydrolyzable ester,biohydrolyzable amide, biohydrolyzable carbamate, solvate, hydrate orprodrug thereof For example, the compound optionally comprises asubstituent that is convertible in vivo to a different substituent suchas a hydrogen.

It is further noted that the compound may be present in a mixture ofstereoisomers (including tautomers), or the compound may comprise asingle stereoisomer.

The present invention also provides a pharmaceutical compositioncomprising as an active ingredient a compound according to any one ofthe above embodiments and variations. In one particular variation, thecomposition is a solid formulation adapted for oral administration. Inanother particular variation, the composition is a liquid formulationadapted for oral administration. In yet another particular variation,the composition is a tablet. In still another particular variation, thecomposition is a liquid formulation adapted for parenteraladministration.

In another of its aspects, there is provided a pharmaceuticalcomposition comprising a compound according to any one of the aboveembodiments and variations, wherein the composition is adapted foradministration by a route selected from the group consisting of orally,parenterally, intraperitoneally, intravenously, intraarterially,transdermally, sublingually, intramuscularly, rectally, transbuccally,intranasally, liposomally, via inhalation, vaginally, intraoccularly,via local delivery (for example by catheter or stent), subcutaneously,intraadiposally, intraarticularly, and intrathecally.

In yet another of its aspects, there is provided a kit comprising acompound of any one of the above embodiments and variations; andinstructions which comprise one or more forms of information selectedfrom the group consisting of indicating a disease state for which thecomposition is to be administered, storage information for thecomposition, dosing information and instructions regarding how toadminister the composition. In one particular variation, the kitcomprises the compound in a multiple dose form.

In still another of its aspects, there is provided an article ofmanufacture comprising a compound of any one of the above embodimentsand variations; and packaging materials. In one variation, the packagingmaterial comprises a container for housing the compound. In oneparticular variation, the container comprises a label indicating one ormore members of the group consisting of a disease state for which thecompound is to be administered, storage information, dosing informationand/or instructions regarding how to administer the compound. In anothervariation, the article of manufacture comprises the compound in amultiple dose form.

In a further of its aspects, there is provided a therapeutic methodcomprising administering a compound of any one of the above embodimentsand variations to a subject.

In another of its aspects, there is provided a method of inhibiting HDACcomprising contacting HDAC with a compound of any one of the aboveembodiments and variations.

In yet another of its aspects, there is provided a method of inhibitingHDAC comprising causing a compound of any one of the above embodimentsand variations to be present in a subject in order to inhibit HDAC invivo.

In a further of its aspects, there is provided a method of inhibitingHDAC comprising administering a first compound to a subject that isconverted in vivo to a second compound wherein the second compoundinhibits HDAC in vivo, the second compound being a compound according toany one of the above embodiments and variations.

In another of its aspects, there is provided a method of treating adisease state for which HDAC possesses activity that contributes to thepathology and/or symptomology of the disease state, the methodcomprising causing a compound of any one of the above embodiments andvariations to be present in a subject in a therapeutically effectiveamount for the disease state.

In yet another of its aspects, there is provided a method of treating adisease state for which HDAC possesses activity that contributes to thepathology and/or symptomology of the disease state, the methodcomprising administering a compound of any one of the above embodimentsand variations to a subject, wherein the compound is present in thesubject in a therapeutically effective amount for the disease state.

In a further of its aspects, there is provided a method of treating adisease state for which HDAC possesses activity that contributes to thepathology and/or symptomology of the disease state, the methodcomprising administering a first compound to a subject that is convertedin vivo to a second compound wherein the second compound inhibits HDACin vivo, the second compound being a compound according to any one ofthe above embodiments and variations.

In still another embodiment, the present invention relates to a methodfor treating cancer comprising administering a compound according to anyone of the above embodiments and variations to a mammalian species inneed thereof. In one variation, the cancer is selected from the groupconsisting of squamous cell carcinoma, astrocytoma, Kaposi's sarcoma,glioblastoma, non small-cell lung cancer, bladder cancer, head and neckcancer, melanoma, ovarian cancer, prostate cancer, breast cancer,small-cell lung cancer, glioma, colorectal cancer, genitourinary cancerand gastrointestinal cancer.

In another embodiment, the present invention relates to a method fortreating inflammation, inflammatory bowel disease, psoriasis, ortransplant rejection, comprising administering a compound according toany one of the above embodiments and variations to a mammalian speciesin need thereof.

In a further embodiment, the present invention relates to a method fortreating arthritis comprising administering a compound according to anyone of the above embodiments and variations to a mammalian species inneed thereof.

In yet another embodiment, the present invention relates to a method fortreating degenerative diseases of the eye comprising administering acompound according to any one of the above embodiments and variations toa mammalian species in need thereof.

In still another embodiment, the present invention relates to a methodfor treating multiple sclerosis, amyotrophic lateral sclerosis, thyroidneoplasm or Alzheimer's disease comprising administering a compoundaccording to any one of the above embodiments and variations to amammalian species in need thereof.

In a further embodiment, the present invention relates to a method fortreating hyperproliferative skin diseases or inflammatory cutaneousdisorders comprising administering a compound according to any one ofthe above embodiments and variations to a mammalian species in needthereof.

In each of the above embodiments and variations, the histone deacetylaseis optionally a Class I histone deacetylase. In particular variations ofeach of the above embodiments and variations, the histone deacetylase isHDAC2 and/or HDAC8.

In still other of its aspects, the present invention relates to methodsof making the HDAC inhibitors of the present invention, as well asintermediates useful for the preparation of such HDAC inhibitors. In oneembodiment, the processes comprise:

reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a reaction product comprising a formulaselected from the group consisting of

wherein

X is a leaving group;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached; and

R₅, R₆ and R₇ are each independently selected from the group consistingof hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)alkyl,heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₆ and R₇ may be takentogether to form a substituted or unsubstituted ring.

In another embodiment, the processes comprise:

reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a reaction product comprising a formula

wherein

n is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and

R₅, R₆ and R₇ are each independently selected from the group consistingof hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₆ and R₇ may be takentogether to form a substituted or unsubstituted ring.

In still another embodiment, the processes comprise:

reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a reaction product comprising a formula

wherein

n is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and

R₅, R₆ and R₇ are each independently selected from the group consistingof hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₆ and R₇ may be takentogether to form a substituted or unsubstituted ring.

In yet another embodiment, the processes comprise:

reacting a compound comprising the formula

with a compound comprising the formulaR—C(O)—X

under conditions that form a reaction product comprising a formula

wherein

p is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

X is a leaving group;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.

In a further embodiment, the processes comprise:

reacting a compound comprising the formula

with a compound comprising the formulaR—C(O)—X

under conditions that form a reaction product comprising a formula

wherein

p is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

X is a leaving group;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃-1₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.

In still a further embodiment, the processes comprise:

reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a reaction product comprising a formula

wherein

n is selected from the group consisting of 0, 1, 2, 3 and 4;

p is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.

In yet a further embodiment, the processes comprise:

reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a reaction product comprising a formula

wherein

n is selected from the group consisting of 0, 1, 2, 3 and 4;

p is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and each R₁₂ is independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.

In another embodiment, the processes comprise:

reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a first reaction product comprising a formula

reacting the first reaction product with a compound comprising theformula

under conditions that form a second reaction product comprising aformula

wherein

n is selected from the group consisting of 0, 1, 2, 3 and 4;

X is a leaving group;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R₁ and R₂ are each independently selected from the group consisting ofhydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring;

R₃ is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

each R₄ is selected from the group consisting of hydrogen, halo, nitro,cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.

In another embodiment, the processes comprise:

reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a first reaction product comprising a formula

reacting the first reaction product with a compound comprising theformula

under conditions that form a second reaction product comprising aformula

wherein

X is a leaving group.

In one variation of the above embodiments, X is halo. In one particularvariation, X is bromo. In another particular variation, X is chloro.

In yet other of its aspects, the present invention relates to compoundsuseful in the preparation of the HDAC inhibitors of the presentinvention. In one embodiment, the compounds comprise:

wherein

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached; and

R₅, R₆ and R₇ are each independently selected from the group consistingof hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₆ and R₇ may be takentogether to form a substituted or unsubstituted ring.

In another embodiment, the compounds comprise:

wherein

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached; and

R₅, R₆ and R₇ are each independently selected from the group consistingof hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₆ and R₇ may be takentogether to form a substituted or unsubstituted ring.

In still another embodiment, the compounds comprise:

wherein

p is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.

In one particular variation of the above embodiment, the compoundscomprise:

In yet another embodiment, the compounds comprise:

wherein

p is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.

In a further embodiment, the compounds comprise:

wherein

p is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.

In still a further embodiment, the compounds comprise:

wherein

p is selected from the group consisting of 0, 1, 2, 3 and 4;

A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted;

L is a linker providing a 0-6 atom separation between the two ring atomsto which L is attached;

R is selected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)heteroaryl,(C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, each substituted orunsubstituted;

R₇ is selected from the group consisting of hydrogen, halo, nitro,cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and

each R₁₂ is independently selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl((C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁I₁ may be takentogether to form a substituted or unsubstituted ring.

Salts, Hydrates, and Prodrugs of HDAC Inhibitors

It should be recognized that the compounds of the present invention maybe present and optionally administered in the form of salts, hydratesand prodrugs that are converted in vivo into the compounds of thepresent invention. For example, it is within the scope of the presentinvention to convert the compounds of the present invention into and usethem in the form of their pharmaceutically acceptable salts derived fromvarious organic and inorganic acids and bases in accordance withprocedures well known in the art.

When the compounds of the present invention possess a free base form,the compounds can be prepared as a pharmaceutically acceptable acidaddition salt by reacting the free base form of the compound with apharmaceutically acceptable inorganic or organic acid, e.g.,hydrohalides such as hydrochloride, hydrobromide, hydroiodide; othermineral acids and their corresponding salts such as sulfate, nitrate,phosphate, etc.; and alkyl and monoarylsulfonates such asethanesulfonate, toluenesulfonate and benzenesulfonate; and otherorganic acids and their corresponding salts such as acetate, tartrate,maleate, succinate, citrate, benzoate, salicylate and ascorbate. Furtheracid addition salts of the present invention include, but are notlimited to: adipate, alginate, arginate, aspartate, bisulfate,bisulfite, bromide, butyrate, camphorate, camphorsulfonate, caprylate,chloride, chlorobenzoate, cyclopentanepropionate, digluconate,dihydrogenphosphate, dinitrobenzoate, dodecylsulfate, fumarate,galacterate (from mucic acid), galacturonate, glucoheptaoate, gluconate,glutamate, glycerophosphate, hemisuccinate, hemisulfate, heptanoate,hexanoate, hippurate, hydrochloride, hydrobromide, hydroiodide,2-hydroxyethanesulfonate, iodide, isethionate, iso-butyrate, lactate,lactobionate, malate, malonate, mandelate, metaphosphate,methanesulfonate, methylbenzoate, monohydrogenphosphate,2-naphthalenesulfonate, nicotinate, nitrate, oxalate, oleate, pamoate,pectinate, persulfate, phenylacetate, 3-phenylpropionate, phosphate,phosphonate and phthalate. It should be recognized that the free baseforms will typically differ from their respective salt forms somewhat inphysical properties such as solubility in polar solvents, but otherwisethe salts are equivalent to their respective free base forms for thepurposes of the present invention.

When the compounds of the present invention possess a free acid form, apharmaceutically acceptable base addition salt can be prepared byreacting the free acid form of the compound with a pharmaceuticallyacceptable inorganic or organic base. Examples of such bases are alkalimetal hydroxides including potassium, sodium and lithium hydroxides;alkaline earth metal hydroxides such as barium and calcium hydroxides;alkali metal alkoxides, e.g., potassium ethanolate and sodiumpropanolate; and various organic bases such as ammonium hydroxide,piperidine, diethanolamine and N-methylglutamine. Also included are thealuminum salts of the compounds of the present invention. Further basesalts of the present invention include, but are not limited to: copper,ferric, ferrous, lithium, magnesium, manganic, manganous, potassium,sodium and zinc salts. Organic base salts include, but are not limitedto, salts of primary, secondary and tertiary amines, substituted aminesincluding naturally occurring substituted amines, cyclic amines andbasic ion exchange resins, e.g., arginine, betaine, caffeine,chloroprocaine, choline, N,N′-dibenzylethylenediamine(benzathine),dicyclohexylamine, diethanolamine, 2-diethylaminoethanol,2-dimethylaminoethanol, ethanolamine, ethylenediamine,N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine,hydrabamine, iso-propylamine, lidocaine, lysine, meglumine,N-methyl-D-glucamine, morpholine, piperazine, piperidine, polyamineresins, procaine, purines, theobromine, triethanolamine, triethylamine,trimethylamine, tripropylamine andtris-(hydroxymethyl)-methylamine(tromethamine). It should be recognizedthat the free acid forms will typically differ from their respectivesalt forms somewhat in physical properties such as solubility in polarsolvents, but otherwise the salts are equivalent to their respectivefree acid forms for the purposes of the present invention.

Compounds of the present invention that comprise basicnitrogen-containing groups may be quaternized with such agents as (C₁₋₄)alkyl halides, e.g., methyl, ethyl, iso-propyl and tert-butyl chlorides,bromides and iodides; di(C₁₋₄)alkyl sulfates, e.g., dimethyl, diethyland diamyl sulfates; (C₁₀₋₁₈) alkyl halides, e.g., decyl, dodecyl,lauryl, myristyl and stearyl chlorides, bromides and iodides; and aryl(C₁₋₄) alkyl halides, e.g., benzyl chloride and phenethyl bromide. Suchsalts permit the preparation of both water-soluble and oil-solublecompounds of the present invention.

N-oxides of compounds according to the present invention can be preparedby methods known to those of ordinary skill in the art. For example,N-oxides can be prepared by treating an unoxidized form of the compoundwith an oxidizing agent (e.g., trifluoroperacetic acid, permaleic acid,perbenzoic acid, peracetic acid, meta-chloroperoxybenzoic acid, or thelike) in a suitable inert organic solvent (e.g., a halogenatedhydrocarbon such as dichloromethane) at approximately 0° C.Alternatively, the N-oxides of the compounds can be prepared from theN-oxide of an appropriate starting material.

Prodrug derivatives of compounds according to the present invention canbe prepared by modifying substituents of compounds of the presentinvention that are then converted in vivo to a different substituent. Itis noted that in many instances, the prodrugs themselves also fallwithin the scope of the range of compounds according to the presentinvention. For example, prodrugs can be prepared by reacting a compoundwith a carbamylating agent (e.g., 1,1-acyloxyalkylcarbonochloridate,para-nitrophenyl carbonate, or the like) or an acylating agent. Furtherexamples of methods of making prodrugs are described in Saulnier etal.(1994), Bioorganic and Medicinal Chemistry Letters, Vol. 4, p. 1985.

Protected derivatives of compounds of the present invention can also bemade. Examples of techniques applicable to the creation of protectinggroups and their removal can be found in T. W. Greene, Protecting Groupsin Organic Synthesis, 3^(rd) edition, John Wiley & Sons, Inc. 1999.

Compounds of the present invention may also be conveniently prepared, orformed during the process of the invention, as solvates (e.g.,hydrates). Hydrates of compounds of the present invention may beconveniently prepared by recrystallization from an aqueous/organicsolvent mixture, using organic solvents such as dioxin, tetrahydrofuranor methanol.

A “pharmaceutically acceptable salt”, as used herein, is intended toencompass any compound according to the present invention that isutilized in the form of a salt thereof, especially where the saltconfers on the compound improved pharmacokinetic properties as comparedto the free form of compound or a different salt form of the compound.The pharmaceutically acceptable salt form may also initially conferdesirable pharmacokinetic properties on the compound that it did notpreviously possess, and may even positively affect the pharmacodynamicsof the compound with respect to its therapeutic activity in the body. Anexample of a pharmacokinetic property that may be favorably affected isthe manner in which the compound is transported across cell membranes,which in turn may directly and positively affect the absorption,distribution, biotransformation and excretion of the compound. While theroute of administration of the pharmaceutical composition is important,and various anatomical, physiological and pathological factors cancritically affect bioavailability, the solubility of the compound isusually dependent upon the character of the particular salt formthereof, which it utilized. One of skill in the art will appreciate thatan aqueous solution of the compound will provide the most rapidabsorption of the compound into the body of a subject being treated,while lipid solutions and suspensions, as well as solid dosage forms,will result in less rapid absorption of the compound.

Preparation of HDAC Inhibitors

Various methods may be developed for synthesizing compounds according tothe present invention. Representative methods for synthesizing thesecompounds are provided in the Examples. It is noted, however, thatcompounds of the present invention may also be synthesized by othersynthetic routes that others may devise.

It will be readily recognized that certain compounds according to thepresent invention have atoms with linkages to other atoms that confer aparticular stereochemistry to the compound (e.g., chiral centers). It isrecognized that synthesis of compounds according to the presentinvention may result in the creation of mixtures of differentstereoisomers (i.e., enantiomers and diastereomers). Unless a particularstereochemistry is specified, recitation of a compound is intended toencompass all of the different possible stereoisomers.

Various methods for separating mixtures of different stereoisomers areknown in the art. For example, a racemic mixture of a compound may bereacted with an optically active resolving agent to form a pair ofdiastereoisomeric compounds. The diastereomers may then be separated inorder to recover the optically pure enantiomers. Dissociable complexesmay also be used to resolve enantiomers (e.g., crystallinediastereoisomeric salts). Diastereomers typically have sufficientlydistinct physical properties (e.g., melting points, boiling points,solubilities, reactivity, etc.) that they can be readily separated bytaking advantage of these dissimilarities. For example, diastereomerscan typically be separated by chromatography or by separation/resolutiontechniques based upon differences in solubility. A more detaileddescription of techniques that can be used to resolve stereoisomers ofcompounds from their racemic mixture can be found in Jean Jacques AndreCollet, Samuel H. Wilen, Enantiomers, Racemates and Resolutions, JohnWiley & Sons, Inc. (1981).

Compositions Comprising HDAC Inhibitors

A wide variety of compositions and administration methods may be used inconjunction with the compounds of the present invention. Suchcompositions may include, in addition to the compounds of the presentinvention, conventional pharmaceutical excipients, and otherconventional, pharmaceutically inactive agents. Additionally, thecompositions may include active agents in addition to the compounds ofthe present invention. These additional active agents may includeadditional compounds according to the invention, and/or one or moreother pharmaceutically active agents.

The compositions may be in gaseous, liquid, semi-liquid or solid form,formulated in a manner suitable for the route of administration to beused. For oral administration, capsules and tablets are typically used.For parenteral administration, reconstitution of a lyophilized powder,prepared as described herein, is typically used.

Compositions comprising compounds of the present invention may beadministered or coadministered orally, parenterally, intraperitoneally,intravenously, intraarterially, transdermally, sublingually,intramuscularly, rectally, transbuccally, intranasally, liposomally, viainhalation, vaginally, intraoccularly, via local delivery (for exampleby catheter or stent), subcutaneously, intraadiposally,intraarticularly, or intrathecally. The compounds and/or compositionsaccording to the invention may also be administered or coadministered inslow release dosage forms.

The HDAC inhibitors and compositions comprising them may be administeredor coadministered in any conventional dosage form. Co-administration inthe context of this invention is intended to mean the administration ofmore than one therapeutic agent, one of which includes a HDAC inhibitor,in the course of a coordinated treatment to achieve an improved clinicaloutcome. Such co-administration may also be coextensive, that is,occurring during overlapping periods of time.

Solutions or suspensions used for parenteral, intradermal, subcutaneous,or topical application may optionally include one or more of thefollowing components: a sterile diluent, such as water for injection,saline solution, fixed oil, polyethylene glycol, glycerine, propyleneglycol or other synthetic solvent; antimicrobial agents, such as benzylalcohol and methyl parabens; antioxidants, such as ascorbic acid andsodium bisulfite; chelating agents, such as ethylenediaminetetraaceticacid (EDTA); buffers, such as acetates, citrates and phosphates; agentsfor the adjustment of tonicity such as sodium chloride or dextrose, andagents for adjusting the acidity or alkalinity of the composition, suchas alkaline or acidifying agents or buffers like carbonates,bicarbonates, phosphates, hydrochloric acid, and organic acids likeacetic and citric acid. Parenteral preparations may optionally beenclosed in ampules, disposable syringes or single or multiple dosevials made of glass, plastic or other suitable material.

When compounds according to the present invention exhibit insufficientsolubility, methods for solubilizing the compounds may be used. Suchmethods are known to those of skill in this art, and include, but arenot limited to, using cosolvents, such as dimethylsulfoxide (DMSO),using surfactants, such as TWEEN, or dissolution in aqueous sodiumbicarbonate. Derivatives of the compounds, such as prodrugs of thecompounds may also be used in formulating effective pharmaceuticalcompositions.

Upon mixing or adding compounds according to the present invention to acomposition, a solution, suspension, emulsion or the like may be formed.The form of the resulting composition will depend upon a number offactors, including the intended mode of administration, and thesolubility of the compound in the selected carrier or vehicle. Theeffective concentration needed to ameliorate the disease being treatedmay be empirically determined.

Compositions according to the present invention are optionally providedfor administration to humans and animals in unit dosage forms, such astablets, capsules, pills, powders, dry powders for inhalers, granules,sterile parenteral solutions or suspensions, and oral solutions orsuspensions, and oil-water emulsions containing suitable quantities ofthe compounds, particularly the pharmaceutically acceptable salts,preferably the sodium salts, thereof. The pharmaceuticallytherapeutically active compounds and derivatives thereof are typicallyformulated and administered in unit-dosage forms or multiple-dosageforms. Unit-dose forms, as used herein, refers to physically discreteunits suitable for human and animal subjects and packaged individuallyas is known in the art. Each unit-dose contains a predetermined quantityof the therapeutically active compound sufficient to produce the desiredtherapeutic effect, in association with the required pharmaceuticalcarrier, vehicle or diluent. Examples of unit-dose forms includeampoules and syringes individually packaged tablet or capsule. Unit-doseforms may be administered in fractions or multiples thereof. Amultiple-dose form is a plurality of identical unit-dosage formspackaged in a single container to be administered in segregatedunit-dose form. Examples of multiple-dose forms include vials, bottlesof tablets or capsules or bottles of pint or gallons. Hence, multipledose form is a multiple of unit-doses that are not segregated inpackaging.

In addition to one or more compounds according to the present invention,the composition may comprise: a diluent such as lactose, sucrose,dicalcium phosphate, or carboxymethylcellulose; a lubricant, such asmagnesium stearate, calcium stearate and talc; and a binder such asstarch, natural gums, such as gum acaciagelatin, glucose, molasses,polvinylpyrrolidine, celluloses and derivatives thereof, povidone,crospovidones and other such binders known to those of skill in the art.Liquid pharmaceutically administrable compositions can, for example, beprepared by dissolving, dispersing, or otherwise mixing an activecompound as defined above and optional pharmaceutical adjuvants in acarrier, such as, for example, water, saline, aqueous dextrose,glycerol, glycols, ethanol, and the like, to form a solution orsuspension. If desired, the pharmaceutical composition to beadministered may also contain minor amounts of auxiliary substances suchas wetting agents, emulsifying agents, or solubilizing agents, pHbuffering agents and the like, for example, acetate, sodium citrate,cyclodextrine derivatives, sorbitan monolaurate, triethanolamine sodiumacetate, triethanolamine oleate, and other such agents. Actual methodsof preparing such dosage forms are known in the art, or will beapparent, to those skilled in this art; for example, see Remington'sPharmaceutical Sciences, Mack Publishing Company, Easton, Pa., 15thEdition, 1975. The composition or formulation to be administered will,in any event, contain a sufficient quantity of a inhibitor of thepresent invention to reduce HDAC activity in vivo, thereby treating thedisease state of the subject.

Dosage forms or compositions may optionally comprise one or morecompounds according to the present invention in the range of 0.005% to100% (weight/weight) with the balance comprising additional substancessuch as those described herein. For oral administration, apharmaceutically acceptable composition may optionally comprise any oneor more commonly employed excipients, such as, for examplepharmaceutical grades of mannitol, lactose, starch, magnesium stearate,talcum, cellulose derivatives, sodium crosscarmellose, glucose, sucrose,magnesium carbonate, sodium saccharin, talcum. Such compositions includesolutions, suspensions, tablets, capsules, powders, dry powders forinhalers and sustained release formulations, such as, but not limitedto, implants and microencapsulated delivery systems, and biodegradable,biocompatible polymers, such as collagen, ethylene vinyl acetate,polyanhydrides, polyglycolic acid, polyorthoesters, polylactic acid andothers. Methods for preparing these formulations are known to thoseskilled in the art. The compositions may optionally contain 0.01%-100%(weight/weight) of one or more HDAC inhibitors, optionally 0.1-95%, andoptionally 1-95%.

Salts, preferably sodium salts, of the inhibitors may be prepared withcarriers that protect the compound against rapid elimination from thebody, such as time release formulations or coatings. The formulationsmay further include other active compounds to obtain desiredcombinations of properties.

Formulations For Oral Administration

Oral pharmaceutical dosage forms may be as a solid, gel or liquid.Examples of solid dosage forms include, but are not limited to tablets,capsules, granules, and bulk powders. More specific examples of oraltablets include compressed, chewable lozenges and tablets that may beenteric-coated, sugar-coated or film-coated. Examples of capsulesinclude hard or soft gelatin capsules. Granules and powders may beprovided in non-effervescent or effervescent forms. Each may be combinedwith other ingredients known to those skilled in the art.

In certain embodiments, compounds according to the present invention areprovided as solid dosage forms, preferably capsules or tablets. Thetablets, pills, capsules, troches and the like may optionally containone or more of the following ingredients, or compounds of a similarnature: a binder; a diluent; a disintegrating agent; a lubricant; aglidant; a sweetening agent; and a flavoring agent.

Examples of binders that may be used include, but are not limited to,microcrystalline cellulose, gum tragacanth, glucose solution, acaciamucilage, gelatin solution, sucrose and starch paste.

Examples of lubricants that may be used include, but are not limited to,talc, starch, magnesium or calcium stearate, lycopodium and stearicacid.

Examples of diluents that may be used include, but are not limited to,lactose, sucrose, starch, kaolin, salt, mannitol and dicalciumphosphate.

Examples of glidants that may be used include, but are not limited to,colloidal silicon dioxide.

Examples of disintegrating agents that may be used include, but are notlimited to, crosscarmellose sodium, sodium starch glycolate, alginicacid, corn starch, potato starch, bentonite, methylcellulose, agar andcarboxymethylcellulose.

Examples of coloring agents that may be used include, but are notlimited to, any of the approved certified water-soluble FD and C dyes,mixtures thereof, and water insoluble FD and C dyes suspended on aluminahydrate.

Examples of sweetening agents that may be used include, but are notlimited to, sucrose, lactose, mannitol and artificial sweetening agentssuch as sodium cyclamate and saccharin, and any number of spray-driedflavors.

Examples of flavoring agents that may be used include, but are notlimited to, natural flavors extracted from plants such as fruits andsynthetic blends of compounds that produce a pleasant sensation, suchas, but not limited to peppermint and methyl salicylate.

Examples of wetting agents that may be used include, but are not limitedto, propylene glycol monostearate, sorbitan monooleate, diethyleneglycol monolaurate and polyoxyethylene lauryl ether.

Examples of anti-emetic coatings that may be used include, but are notlimited to, fatty acids, fats, waxes, shellac, ammoniated shellac andcellulose acetate phthalates.

Examples of film coatings that may be used include, but are not limitedto, hydroxyethylcellulose, sodium carboxymethylcellulose, polyethyleneglycol 4000 and cellulose acetate phthalate.

If oral administration is desired, the salt of the compound mayoptionally be provided in a composition that protects it from the acidicenvironment of the stomach. For example, the composition can beformulated in an enteric coating that maintains its integrity in thestomach and releases the active compound in the intestine. Thecomposition may also be formulated in combination with an antacid orother such ingredient.

When the dosage unit form is a capsule, it may optionally additionallycomprise a liquid carrier such as a fatty oil. In addition, dosage unitforms may optionally additionally comprise various other materials thatmodify the physical form of the dosage unit, for example, coatings ofsugar and other enteric agents.

Compounds according to the present invention may also be administered asa component of an elixir, suspension, syrup, wafer, sprinkle, chewinggum or the like. A syrup may optionally comprise, in addition to theactive compounds, sucrose as a sweetening agent and certainpreservatives, dyes and colorings and flavors.

The compounds of the present invention may also be mixed with otheractive materials that do not impair the desired action, or withmaterials that supplement the desired action, such as antacids, H2blockers, and diuretics. For example, if a compound is used for treatingasthma or hypertension, it may be used with other bronchodilators andantihypertensive agents, respectively.

Examples of pharmaceutically acceptable carriers that may be included intablets comprising compounds of the present invention include, but arenot limited to binders, lubricants, diluents, disintegrating agents,coloring agents, flavoring agents, and wetting agents. Enteric-coatedtablets, because of the enteric-coating, resist the action of stomachacid and dissolve or disintegrate in the neutral or alkaline intestines.Sugar-coated tablets may be compressed tablets to which different layersof pharmaceutically acceptable substances are applied. Film-coatedtablets may be compressed tablets that have been coated with polymers orother suitable coating. Multiple compressed tablets may be compressedtablets made by more than one compression cycle utilizing thepharmaceutically acceptable substances previously mentioned. Coloringagents may also be used in tablets. Flavoring and sweetening agents maybe used in tablets, and are especially useful in the formation ofchewable tablets and lozenges.

Examples of liquid oral dosage forms that may be used include, but arenot limited to, aqueous solutions, emulsions, suspensions, solutionsand/or suspensions reconstituted from non-effervescent granules andeffervescent preparations reconstituted from effervescent granules.

Examples of aqueous solutions that may be used include, but are notlimited to, elixirs and syrups. As used herein, elixirs refer to clear,sweetened, hydroalcoholic preparations. Examples of pharmaceuticallyacceptable carriers that may be used in elixirs include, but are notlimited to solvents. Particular examples of solvents that may be usedinclude glycerin, sorbitol, ethyl alcohol and syrup. As used herein,syrups refer to concentrated aqueous solutions of a sugar, for example,sucrose. Syrups may optionally further comprise a preservative.

Emulsions refer to two-phase systems in which one liquid is dispersed inthe form of small globules throughout another liquid. Emulsions mayoptionally be oil-in-water or water-in-oil emulsions. Examples ofpharmaceutically acceptable carriers that may be used in emulsionsinclude, but are not limited to non-aqueous liquids, emulsifying agentsand preservatives.

Examples of pharmaceutically acceptable substances that may be used innon-effervescent granules, to be reconstituted into a liquid oral dosageform, include diluents, sweeteners and wetting agents.

Examples of pharmaceutically acceptable substances that may be used ineffervescent granules, to be reconstituted into a liquid oral dosageform, include organic acids and a source of carbon dioxide.

Coloring and flavoring agents may optionally be used in all of the abovedosage forms.

Particular examples of preservatives that may be used include glycerin,methyl and propylparaben, benzoic add, sodium benzoate and alcohol.

Particular examples of non-aqueous liquids that may be used in emulsionsinclude mineral oil and cottonseed oil.

Particular examples of emulsifying agents that may be used includegelatin, acacia, tragacanth, bentonite, and surfactants such aspolyoxyethylene sorbitan monooleate.

Particular examples of suspending agents that may be used include sodiumcarboxymethylcellulose, pectin, tragacanth, Veegum and acacia. Diluentsinclude lactose and sucrose. Sweetening agents include sucrose, syrups,glycerin and artificial sweetening agents such as sodium cyclamate andsaccharin.

Particular examples of wetting agents that may be used include propyleneglycol monostearate, sorbitan monooleate, diethylene glycol monolaurateand polyoxyethylene lauryl ether.

Particular examples of organic acids that may be used include citric andtartaric acid.

Sources of carbon dioxide that may be used in effervescent compositionsinclude sodium bicarbonate and sodium carbonate. Coloring agents includeany of the approved certified water soluble FD and C dyes, and mixturesthereof.

Particular examples of flavoring agents that may be used include naturalflavors extracted from plants such fruits, and synthetic blends ofcompounds that produce a pleasant taste sensation.

For a solid dosage form, the solution or suspension, in for examplepropylene carbonate, vegetable oils or triglycerides, is preferablyencapsulated in a gelatin capsule. Such solutions, and the preparationand encapsulation thereof, are disclosed in U.S. Pat. Nos. 4,328,245;4,409,239; and 4,410,545. For a liquid dosage form, the solution, e.g.,for example, in a polyethylene glycol, may be diluted with a sufficientquantity of a pharmaceutically acceptable liquid carrier, e.g., water,to be easily measured for administration.

Alternatively, liquid or semi-solid oral formulations may be prepared bydissolving or dispersing the active compound or salt in vegetable oils,glycols, triglycerides, propylene glycol esters (e.g., propylenecarbonate) and other such carriers, and encapsulating these solutions orsuspensions in hard or soft gelatin capsule shells. Other usefulformulations include those set forth in U.S. Pat. Nos. Re 28,819 and4,358,603.

Injectables, Solutions, and Emulsions

The present invention is also directed to compositions designed toadminister the compounds of the present invention by parenteraladministration, generally characterized by subcutaneous, intramuscularor intravenous injection. Injectables may be prepared in anyconventional form, for example as liquid solutions or suspensions, solidforms suitable for solution or suspension in liquid prior to injection,or as emulsions.

Examples of excipients that may be used in conjunction with injectablesaccording to the present invention include, but are not limited towater, saline, dextrose, glycerol or ethanol. The injectablecompositions may also optionally comprise minor amounts of non-toxicauxiliary substances such as wetting or emulsifying agents, pH bufferingagents, stabilizers, solubility enhancers, and other such agents, suchas for example, sodium acetate, sorbitan monolaurate, triethanolamineoleate and cyclodextrins. Implantation of a slow-release orsustained-release system, such that a constant level of dosage ismaintained (see, e.g., U.S. Pat. No. 3,710,795) is also contemplatedherein. The percentage of active compound contained in such parenteralcompositions is highly dependent on the specific nature thereof, as wellas the activity of the compound and the needs of the subject.

Parenteral administration of the formulations includes intravenous,subcutaneous and intramuscular administrations. Preparations forparenteral administration include sterile solutions ready for injection,sterile dry soluble products, such as the lyophilized powders describedherein, ready to be combined with a solvent just prior to use, includinghypodermic tablets, sterile suspensions ready for injection, sterile dryinsoluble products ready to be combined with a vehicle just prior to useand sterile emulsions. The solutions may be either aqueous ornonaqueous.

When administered intravenously, examples of suitable carriers include,but are not limited to physiological saline or phosphate buffered saline(PBS), and solutions containing thickening and solubilizing agents, suchas glucose, polyethylene glycol, and polypropylene glycol and mixturesthereof.

Examples of pharmaceutically acceptable carriers that may optionally beused in parenteral preparations include, but are not limited to aqueousvehicles, nonaqueous vehicles, antimicrobial agents, isotonic agents,buffers, antioxidants, local anesthetics, suspending and dispersingagents, emulsifying agents, sequestering or chelating agents and otherpharmaceutically acceptable substances.

Examples of aqueous vehicles that may optionally be used include SodiumChloride Injection, Ringers Injection, Isotonic Dextrose Injection,Sterile Water Injection, Dextrose and Lactated Ringers Injection.

Examples of nonaqueous parenteral vehicles that may optionally be usedinclude fixed oils of vegetable origin, cottonseed oil, corn oil, sesameoil and peanut oil.

Antimicrobial agents in bacteriostatic or fungistatic concentrations maybe added to parenteral preparations, particularly when the preparationsare packaged in multiple-dose containers and thus designed to be storedand multiple aliquots to be removed. Examples of antimicrobial agentsthat may be used include phenols or cresols, mercurials, benzyl alcohol,chlorobutanol, methyl and propyl p-hydroxybenzoic acid esters,thimerosal, benzalkonium chloride and benzethonium chloride.

Examples of isotonic agents that may be used include sodium chloride anddextrose. Examples of buffers that may be used include phosphate andcitrate. Examples of antioxidants that may be used include sodiumbisulfate. Examples of local anesthetics that may be used includeprocaine hydrochloride. Examples of suspending and dispersing agentsthat may be used include sodium carboxymethylcellulose, hydroxypropylmethylcellulose and polyvinylpyrrolidone. Examples of emulsifying agentsthat may be used include Polysorbate 80 (TWEEN 80). A sequestering orchelating agent of metal ions include EDTA.

Pharmaceutical carriers may also optionally include ethyl alcohol,polyethylene glycol and propylene glycol for water miscible vehicles andsodium hydroxide, hydrochloric acid, citric acid or lactic acid for pHadjustment.

The concentration of an inhibitor in the parenteral formulation may beadjusted so that an injection administers a pharmaceutically effectiveamount sufficient to produce the desired pharmacological effect. Theexact concentration of an inhibitor and/or dosage to be used willultimately depend on the age, weight and condition of the patient oranimal as is known in the art.

Unit-dose parenteral preparations may be packaged in an ampoule, a vialor a syringe with a needle. All preparations for parenteraladministration should be sterile, as is known and practiced in the art.

Injectables may be designed for local and systemic administration.Typically a therapeutically effective dosage is formulated to contain aconcentration of at least about 0.1% w/w up to about 90% w/w or more,preferably more than 1% w/w of the HDAC inhibitor to the treatedtissue(s). The inhibitor may be administered at once, or may be dividedinto a number of smaller doses to be administered at intervals of time.It is understood that the precise dosage and duration of treatment willbe a function of the location of where the composition is parenterallyadministered, the carrier and other variables that may be determinedempirically using known testing protocols or by extrapolation from invivo or in vitro test data. It is to be noted that concentrations anddosage values may also vary with the age of the individual treated. Itis to be further understood that for any particular subject, specificdosage regimens may need to be adjusted over time according to theindividual need and the professional judgment of the personadministering or supervising the administration of the formulations.Hence, the concentration ranges set forth herein are intended to beexemplary and are not intended to limit the scope or practice of theclaimed formulations.

The HDAC inhibitor may optionally be suspended in micronized or othersuitable form or may be derivatized to produce a more soluble activeproduct or to produce a prodrug. The form of the resulting mixturedepends upon a number of factors, including the intended mode ofadministration and the solubility of the compound in the selectedcarrier or vehicle. The effective concentration is sufficient forameliorating the symptoms of the disease state and may be empiricallydetermined.

Lyophilized Powders

The compounds of the present invention may also be prepared aslyophilized powders, which can be reconstituted for administration assolutions, emulsions and other mixtures. The lyophilized powders mayalso be formulated as solids or gels.

Sterile, lyophilized powder may be prepared by dissolving the compoundin a sodium phosphate buffer solution containing dextrose or othersuitable excipient. Subsequent sterile filtration of the solutionfollowed by lyophilization under standard conditions known to those ofskill in the art provides the desired formulation. Briefly, thelyophilized powder may optionally be prepared by dissolving dextrose,sorbitol, fructose, corn syrup, xylitol, glycerin, glucose, sucrose orother suitable agent, about 1-20%, preferably about 5 to 15%, in asuitable buffer, such as citrate, sodium or potassium phosphate or othersuch buffer known to those of skill in the art at, typically, aboutneutral pH. Then, a HDAC inhibitor is added to the resulting mixture,preferably above room temperature, more preferably at about 30-35° C.,and stirred until it dissolves. The resulting mixture is diluted byadding more buffer to a desired concentration. The resulting mixture issterile filtered or treated to remove particulates and to insuresterility, and apportioned into vials for lyophilization. Each vial maycontain a single dosage or multiple dosages of the inhibitor.

Topical Administration

The compounds of the present invention may also be administered astopical mixtures. Topical mixtures may be used for local and systemicadministration. The resulting mixture may be a solution, suspension,emulsions or the like and are formulated as creams, gels, ointments,emulsions, solutions, elixirs, lotions, suspensions, tinctures, pastes,foams, aerosols, irrigations, sprays, suppositories, bandages, dermalpatches or any other formulations suitable for topical administration.

The HDAC inhibitors may be formulated as aerosols for topicalapplication, such as by inhalation (see, U.S. Pat. Nos. 4,044,126,4,414,209, and 4,364,923, which describe aerosols for delivery of asteroid useful for treatment of inflammatory diseases, particularlyasthma). These formulations for administration to the respiratory tractcan be in the form of an aerosol or solution for a nebulizer, or as amicrofine powder for insufflation, alone or in combination with an inertcarrier such as lactose. In such a case, the particles of theformulation will typically have diameters of less than 50 microns,preferably less than 10 microns.

The inhibitors may also be formulated for local or topical application,such as for topical application to the skin and mucous membranes, suchas in the eye, in the form of gels, creams, and lotions and forapplication to the eye or for intracisternal or intraspinal application.Topical administration is contemplated for transdermal delivery and alsofor administration to the eyes or mucosa, or for inhalation therapies.Nasal solutions of the HDAC inhibitor alone or in combination with otherpharmaceutically acceptable excipients can also be administered.

Formulations for Other Routes of Administrations

Depending upon the disease state being treated, other routes ofadministration, such as topical application, transdermal patches, andrectal administration, may also be used. For example, pharmaceuticaldosage forms for rectal administration are rectal suppositories,capsules and tablets for systemic effect. Rectal suppositories are usedherein mean solid bodies for insertion into the rectum that melt orsoften at body temperature releasing one or more pharmacologically ortherapeutically active ingredients. Pharmaceutically acceptablesubstances utilized in rectal suppositories are bases or vehicles andagents to raise the melting point. Examples of bases include cocoabutter (theobroma oil), glycerin-gelatin, carbowax, (polyoxyethyleneglycol) and appropriate mixtures of mono-, di- and triglycerides offatty acids. Combinations of the various bases may be used. Agents toraise the melting point of suppositories include spermaceti and wax.Rectal suppositories may be prepared either by the compressed method orby molding. The typical weight of a rectal suppository is about 2 to 3gm. Tablets and capsules for rectal administration may be manufacturedusing the same pharmaceutically acceptable substance and by the samemethods as for formulations for oral administration.

Examples of Formulations

The following are particular examples of oral, intravenous and tabletformulations that may optionally be used with compounds of the presentinvention. It is noted that these formulations may be varied dependingon the particular compound being used and the indication for which theformulation is going to be used. ORAL FORMULATION Compound of thePresent Invention 10-100 mg Citric Acid Monohydrate 105 mg SodiumHydroxide 18 mg Flavoring Water q.s. to 100 mL

INTRAVENOUS FORMULATION Compound of the Present Invention 0.1-10 mgDextrose Monohydrate q.s. to make isotonic Citric Acid Monohydrate 1.05mg Sodium Hydroxide 0.18 mg Water for Injection q.s. to 1.0 mL

TABLET FORMULATION Compound of the Present Invention  1%Microcrystalline Cellulose 73% Stearic Acid 25% Colloidal Silica   1%.Kits Comprising HDAC Inhibitors

The invention is also directed to kits and other articles of manufacturefor treating diseases associated with HDACs. It is noted that diseasesare intended to cover all conditions for which the HDACs possessactivity that contributes to the pathology and/or symptomology of thecondition.

In one embodiment, a kit is provided that comprises a compositioncomprising at least one inhibitor of the present invention incombination with instructions. The instructions may indicate the diseasestate for which the composition is to be administered, storageinformation, dosing information and/or instructions regarding how toadminister the composition. The kit may also comprise packagingmaterials. The packaging material may comprise a container for housingthe composition. The kit may also optionally comprise additionalcomponents, such as syringes for administration of the composition. Thekit may comprise the composition in single or multiple dose forms.

In another embodiment, an article of manufacture is provided thatcomprises a composition comprising at least one inhibitor of the presentinvention in combination with packaging materials. The packagingmaterial may comprise a container for housing the composition. Thecontainer may optionally comprise a label indicating the disease statefor which the composition is to be administered, storage information,dosing information and/or instructions regarding how to administer thecomposition. The kit may also optionally comprise additional components,such as syringes for administration of the composition. The kit maycomprise the composition in single or multiple dose forms.

It is noted that the packaging material used in kits and articles ofmanufacture according to the present invention may form a plurality ofdivided containers such as a divided bottle or a divided foil packet.The container can be in any conventional shape or form as known in theart which is made of a pharmaceutically acceptable material, for examplea paper or cardboard box, a glass or plastic bottle or jar, are-sealable bag (for example, to hold a ∫refill” of tablets forplacement into a different container), or a blister pack with individualdoses for pressing out of the pack according to a therapeutic schedule.The container that is employed will depend on the exact dosage forminvolved, for example a conventional cardboard box would not generallybe used to hold a liquid suspension. It is feasible that more than onecontainer can be used together in a single package to market a singledosage form. For example, tablets may be contained in a bottle that isin turn contained within a box. Typically the kit includes directionsfor the administration of the separate components. The kit form isparticularly advantageous when the separate components are preferablyadministered in different dosage forms (e.g., oral, topical, transdermaland parenteral), are administered at different dosage intervals, or whentitration of the individual components of the combination is desired bythe prescribing physician.

One particular example of a kit according to the present invention is aso-called blister pack. Blister packs are well known in the packagingindustry and are being widely used for the packaging of pharmaceuticalunit dosage forms (tablets, capsules, and the like). Blister packsgenerally consist of a sheet of relatively stiff material covered with afoil of a preferably transparent plastic material. During the packagingprocess recesses are formed in the plastic foil. The recesses have thesize and shape of individual tablets or capsules to be packed or mayhave the size and shape to accommodate multiple tablets and/or capsulesto be packed. Next, the tablets or capsules are placed in the recessesaccordingly and the sheet of relatively stiff material is sealed againstthe plastic foil at the face of the foil which is opposite from thedirection in which the recesses were formed. As a result, the tablets orcapsules are individually sealed or collectively sealed, as desired, inthe recesses between the plastic foil and the sheet. Preferably thestrength of the sheet is such that the tablets or capsules can beremoved from the blister pack by manually applying pressure on therecesses whereby an opening is formed in the sheet at the place of therecess. The tablet or capsule can then be removed via said opening.

Another specific embodiment of a kit is a dispenser designed to dispensethe daily doses one at a time in the order of their intended use.Preferably, the dispenser is equipped with a memory-aid, so as tofurther facilitate compliance with the regimen. An example of such amemory-aid is a mechanical counter that indicates the number of dailydoses that has been dispensed. Another example of such a memory-aid is abattery-powered micro-chip memory coupled with a liquid crystal readout,or audible reminder signal which, for example, reads out the date thatthe last daily dose has been taken and/or reminds one when the next doseis to be taken.

Combination Therapy

A wide variety of therapeutic agents may have a therapeutic additive orsynergistic effect with HDAC inhibitors according to the presentinvention. Such therapeutic agents may additively or synergisticallycombine with the HDAC inhibitors to inhibit undesirable cell growth,such as inappropriate cell growth resulting in undesirable benignconditions or tumor growth.

In one embodiment, a method is provided for treating a cellproliferative disease state comprising treating cells with a compoundaccording to the present invention in combination with ananti-proliferative agent, wherein the cells are treated with thecompound according to the present invention before, at the same time,and/or after the cells are treated with the anti-proliferative agent,referred to herein as combination therapy. It is noted that treatment ofone agent before another is referred to herein as sequential therapy,even if the agents are also administered together. It is noted thatcombination therapy is intended to cover when agents are administeredbefore or after each other (sequential therapy) as well as when theagents are administered at the same time.

Examples of therapeutic agents that may be used in combination with HDACinhibitors include, but are not limited to, anticancer agents,alkylating agents, antibiotic agents, antimetabolic agents, hormonalagents, plant-derived agents, and biologic agents.

Alkylating agents are polyfunctional compounds that have the ability tosubstitute alkyl groups for hydrogen ions. Examples of alkylating agentsinclude, but are not limited to, bischloroethylamines (nitrogenmustards, e.g. chlorambucil, cyclophosphamide, ifosfamide,mechlorethamine, melphalan, uracil mustard), aziridines (e.g. thiotepa),alkyl alkone sulfonates (e.g. busulfan), nitrosoureas (e.g. carmustine,lomustine, streptozocin), nonclassic alkylating agents (altretamine,dacarbazine, and procarbazine), platinum compounds (carboplastin andcisplatin). These compounds react with phosphate, amino, hydroxyl,sulfihydryl, carboxyl, and imidazole groups. Under physiologicalconditions, these drugs ionize and produce positively charged ion thatattach to susceptible nucleic acids and proteins, leading to cell cyclearrest and/or cell death. Combination therapy including a HDAC inhibitorand an alkylating agent may have therapeutic synergistic effects oncancer and reduce sides affects associated with these chemotherapeuticagents.

Antibiotic agents are a group of drugs that produced in a manner similarto antibiotics as a modification of natural products. Examples ofantibiotic agents include, but are not limited to, anthracyclines (e.g.doxorubicin, daunorubicin, epirubicin, idarubicin and anthracenedione),mitomycin C, bleomycin, dactinomycin, plicatomycin. These antibioticagents interfere with cell growth by targeting different cellularcomponents. For example, anthracyclines are generally believed tointerfere with the action of DNA topoisomerase II in the regions oftranscriptionally active DNA, which leads to DNA strand scissions.Bleomycin is generally believed to chelate iron and forms an activatedcomplex, which then binds to bases of DNA, causing strand scissions andcell death. Combination therapy including a HDAC inhibitor and anantibiotic agent may have therapeutic synergistic effects on cancer andreduce sides affects associated with these chemotherapeutic agents.

Antimetabolic agents are a group of drugs that interfere with metabolicprocesses vital to the physiology and proliferation of cancer cells.Actively proliferating cancer cells require continuous synthesis oflarge quantities of nucleic acids, proteins, lipids, and other vitalcellular constituents. Many of the antimetabolites inhibit the synthesisof purine or pyrimidine nucleosides or inhibit the enzymes of DNAreplication. Some antimetabolites also interfere with the synthesis ofribonucleosides and RNA and/or amino acid metabolism and proteinsynthesis as well. By interfering with the synthesis of vital cellularconstituents, antimetabolites can delay or arrest the growth of cancercells. Examples of antimetabolic agents include, but are not limited to,fluorouracil (5-FU), floxuridine (5-FUdR), methotrexate, leucovorin,hydroxyurea, thioguanine (6-TG), mercaptopurine (6-MP), cytarabine,pentostatin, fludarabine phosphate, cladribine (2-CDA), asparaginase,and gemcitabine. Combination therapy including a HDAC inhibitor and aantimetabolic agent may have therapeutic synergistic effects on cancerand reduce sides affects associated with these chemotherapeutic agents.

Hormonal agents are a group of drug that regulate the growth anddevelopment of their target organs. Most of the hormonal agents are sexsteroids and their derivatives and analogs thereof, such as estrogens,androgens, and progestins. These hormonal agents may serve asantagonists of receptors for the sex steroids to down regulate receptorexpression and transcription of vital genes. Examples of such hormonalagents are synthetic estrogens (e.g. diethylstibestrol), antiestrogens(e.g. tamoxifen, toremifene, fluoxymesterol and raloxifene),antiandrogens (bicalutamide, nilutamide, flutamide), aromataseinhibitors (e.g., aminoglutethimide, anastrozole and tetrazole),ketoconazole, goserelin acetate, leuprolide, megestrol acetate andmifepristone. Combination therapy including a HDAC inhibitor and ahormonal agent may have therapeutic synergistic effects on cancer andreduce sides affects associated with these chemotherapeutic agents.

Plant-derived agents are a group of drugs that are derived from plantsor modified based on the molecular structure of the agents. Examples ofplant-derived agents include, but are not limited to, vinca alkaloids(e.g., vincristine, vinblastine, vindesine, vinzolidine andvinorelbine), podophyllotoxins (e.g., etoposide (VP-16) and teniposide(VM-26)), taxanes (e.g., paclitaxel and docetaxel). These plant-derivedagents generally act as antimitotic agents that bind to tubulin andinhibit mitosis. Podophyllotoxins such as etoposide are believed tointerfere with DNA synthesis by interacting with topoisomerase TI,leading to DNA strand scission. Combination therapy including a HDACinhibitor and a plant-derived agent may have therapeutic synergisticeffects on cancer and reduce sides affects associated with thesechemotherapeutic agents.

Biologic agents are a group of biomolecules that elicit cancer/tumorregression when used alone or in combination with chemotherapy and/orradiotherapy. Examples of biologic agents include, but are not limitedto, immuno-modulating proteins such as cytokines, monoclonal antibodiesagainst tumor antigens, tumor suppressor genes, and cancer vaccines.Combination therapy including a HDAC inhibitor and a biologic agent mayhave therapeutic synergistic effects on cancer, enhance the patient'simmune responses to tumorigenic signals, and reduce potential sidesaffects associated with this chemotherapeutic agent.

Cytokines possess profound immunomodulatory activity. Some cytokinessuch as interleukin-2 (IL-2, aldesleukin) and interferon havedemonstrated antitumor activity and have been approved for the treatmentof patients with metastatic renal cell carcinoma and metastaticmalignant melanoma. IL-2 is a T-cell growth factor that is central toT-cell-mediated immune responses. The selective antitumor effects ofIL-2 on some patients are believed to be the result of a cell-mediatedimmune response that discriminate between self and nonself. Examples ofinterleukins that may be used in conjunction with HDAC inhibitorinclude, but are not limited to, interleukin 2 (IL-2), and interleukin 4(IL-4), interleukin 12 (IL-12).

Interferon. include more than 23 related subtypes with overlappingactivities, all of the IFN subtypes within the scope of the presentinvention. IFN has demonstrated activity against many solid andhematologic malignancies, the later appearing to be particularlysensitive.

Other cytokines that may be used in conjunction with a HDAC inhibitorinclude those cytokines that exert profound effects on hematopoiesis andimmune functions. Examples of such cytokines include, but are notlimited to erythropoietin, granulocyte-CSF (filgrastin), andgranulocyte, macrophage-CSF (sargramostim). These cytokines may be usedin conjunction with a HDAC inhibitor to reduce chemotherapy-inducedmyelopoietic toxicity.

Other immuno-modulating agents other than cytokines may also be used inconjunction with a HDAC inhibitor to inhibit abnormal cell growth.Examples of such immuno-modulating agents include, but are not limitedto bacillus Calmette-Guerin, levamisole, and octreotide, a long-actingoctapeptide that mimics the effects of the naturally occurring hormonesomatostatin.

Monoclonal antibodies against tumor antigens are antibodies elicitedagainst antigens expressed by tumors, preferably tumor-specificantigens. For example, monoclonal antibody HERCEPTIN® (Trastruzumab) israised against human epidermal growth factor receptor2 (HER2) that isoverexpressed in some breast tumors including metastatic breast cancer.Overexpression of HER2 protein is associated with more aggressivedisease and poorer prognosis in the clinic. HERCEPTIN® is used as asingle agent for the treatment of patients with metastatic breast cancerwhose tumors over express the HER2 protein. Combination therapyincluding HDAC inhibitor and HERCEPTIN® may have therapeutic synergisticeffects on tumors, especially on metastatic cancers.

Another example of monoclonal antibodies against tumor antigens isRITUXAN® (Rituximab) that is raised against CD20 on lymphoma cells andselectively deplete normal and malignant CD20+ pre-B and mature B cells.RITUXAN® is used as single agent for the treatment of patients withrelapsed or refractory low-grade or follicular, CD20+, B cellnon-Hodgkin's lymphoma. Combination therapy including HDAC inhibitor andRITUXAN® may have therapeutic synergistic effects not only on lymphoma,but also on other forms or types of malignant tumors.

Tumor suppressor genes are genes that function to inhibit the cellgrowth and division cycles, thus preventing the development ofneoplasia. Mutations in tumor suppressor genes cause the cell to ignoreone or more of the components of the network of inhibitory signals,overcoming the cell cycle check points and resulting in a higher rate ofcontrolled cell growth-cancer. Examples of the tumor suppressor genesinclude, but are not limited to, DPC-4, NF-1, NF-2, RB, p53, WT1, BRCA1and BRCA2.

DPC-4 is involved in pancreatic cancer and participates in a cytoplasmicpathway that inhibits cell division. NF-1 codes for a protein thatinhibits Ras, a cytoplasmic inhibitory protein. NF-1 is involved inneurofibroma and pheochromocytomas of the nervous system and myeloidleukemia. NF-2 encodes a nuclear protein that is involved in meningioma,schwanoma, and ependymoma of the nervous system. RB codes for the pRBprotein, a nuclear protein that is a major inhibitor of cell cycle. RBis involved in retinoblastoma as well as bone, bladder, small cell lungand breast cancer. P53 codes for p53 protein that regulates celldivision and can induce apoptosis. Mutation and/or inaction of p53 isfound in a wide ranges of cancers. WT1 is involved in Wilms tumor of thekidneys. BRCA1 is involved in breast and ovarian cancer, and BRCA2 isinvolved in breast cancer. The tumor suppressor gene can be transferredinto the tumor cells where it exerts its tumor suppressing functions.Combination therapy including a HDAC inhibitor and a tumor suppressormay have therapeutic synergistic effects on patients suffering fromvarious forms of cancers.

Cancer vaccines are a group of agents that induce the body's specificimmune response to tumors. Most of cancer vaccines under research anddevelopment and clinical trials are tumor-associated antigens (TAAs).TAA are structures (i.e. proteins, enzymes or carbohydrates) which arepresent on tumor cells and relatively absent or diminished on normalcells. By virtue of being fairly unique to the tumor cell, TAAs providetargets for the immune system to recognize and cause their destruction.Example of TAAs include, but are not limited to gangliosides (GM2),prostate specific antigen (PSA), alpha-fetoprotein (AFP),carcinoembryonic antigen (CEA) (produced by colon cancers and otheradenocarcinomas, e.g. breast, lung, gastric, and pancreas cancer s),melanoma associated antigens (MART-1, gp 100, MAGE 1,3 tyrosinase),papillomavirus E6 and E7 fragments, whole cells or portions/lysates ofantologous tumor cells and allogeneic tumor cells.

An adjuvant may be used to augment the immune response to TAAs. Examplesof adjuvants include, but are not limited to, bacillus Calmette-Guerin(BCG), endotoxin lipopolysaccharides, keyhole limpet hemocyanin (GKLH),interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor(GM-CSF) and cytoxan, a chemotherapeutic agent which is believe toreduce tumor-induced suppression when given in low doses.

EXAMPLES

Preparation of HDAC Inhibitors

Various methods may be developed for synthesizing compounds according tothe present invention. Representative methods for synthesizing thesecompounds are provided in the Examples. It is noted, however, that thecompounds of the present invention may also be synthesized by othersynthetic routes that others may devise.

It will be readily recognized that certain compounds according to thepresent invention have atoms with linkages to other atoms that confer aparticular stereochemistry to the compound (e.g., chiral centers). It isrecognized that synthesis of compounds according to the presentinvention may result in the creation of mixtures of differentstereoisomers (i.e., enantiomers and diastereomers). Unless a particularstereochemistry is specified, recitation of a compound is intended toencompass all of the different possible stereoisomers.

Various methods for separating mixtures of different stereoisomers areknown in the art. For example, a racemic mixture of a compound may bereacted with an optically active resolving agent to form a pair ofdiastereoisomeric compounds. The diastereomers may then be separated inorder to recover the optically pure enantiomers. Dissociable complexesmay also be used to resolve enantiomers (e.g., crystallinediastereoisomeric salts). Diastereomers typically have sufficientlydistinct physical properties (e.g., melting points, boiling points,solubilities, reactivity, etc.) and can be readily separated by takingadvantage of these dissimilarities. For example, diastereomers cantypically be separated by chromatography or by separation/resolutiontechniques based upon differences in solubility. A more detaileddescription of techniques that can be used to resolve stereoisomers ofcompounds from their racemic mixture can be found in Jean Jacques AndreCollet, Samuel H. Wilen, Enantiomers, Racemates and Resolutions, JohnWiley & Sons, Inc. (1981).

Compounds according to the present invention can also be prepared as apharmaceutically acceptable acid addition salt by reacting the free baseform of the compound with a pharmaceutically acceptable inorganic ororganic acid. Alternatively, a pharmaceutically acceptable base additionsalt of a compound can be prepared by reacting the free acid form of thecompound with a pharmaceutically acceptable inorganic or organic base.Inorganic and organic acids and bases suitable for the preparation ofthe pharmaceutically acceptable salts of compounds are set forth in thedefinitions section of this Application. Alternatively, the salt formsof the compounds can be prepared using salts of the starting materialsor intermediates.

The free acid or free base forms of the compounds can be prepared fromthe corresponding base addition salt or acid addition salt form. Forexample, a compound in an acid addition salt form can be converted tothe corresponding free base by treating with a suitable base (e.g.,ammonium hydroxide solution, sodium hydroxide, and the like). A compoundin a base addition salt form can be converted to the corresponding freeacid by treating with a suitable acid (e.g., hydrochloric acid, etc).

The N-oxides of compounds according to the present invention can beprepared by methods known to those of ordinary skill in the art. Forexample, N-oxides can be prepared by treating an unoxidized form of thecompound with an oxidizing agent (e.g., trifluoroperacetic acid,permaleic acid, perbenzoic acid, peracetic acid,meta-chloroperoxybenzoic acid, or the like) in a suitable inert organicsolvent (e.g., a halogenated hydrocarbon such as dichloromethane) atapproximately 0 C. Alternatively, the N-oxides of the compounds can beprepared from the N-oxide of an appropriate starting material.

Compounds in an unoxidized form can be prepared from N-oxides ofcompounds by treating with a reducing agent (e.g., sulfur, sulfurdioxide, triphenyl phosphine, lithium borohydride, sodium borohydride,phosphorus trichloride, tribromide, or the like) in an suitable inertorganic solvent (e.g., acetonitrile, ethanol, aqueous dioxane, or thelike) at 0 to 80° C.

Prodrug derivatives of the compounds can be prepared by methods known tothose of ordinary skill in the art (e.g., for further details seeSaulnier et al.(1994), Bioorganic and Medicinal Chemistry Letters, Vol.4, p. 1985). For example, appropriate prodrugs can be prepared byreacting a non-derivatized compound with a suitable carbamylating agent(e.g., 1,1-acyloxyalkylcarbonochloridate, para-nitrophenyl carbonate, orthe like).

Protected derivatives of the compounds can be made by methods known tothose of ordinary skill in the art. A detailed description of thetechniques applicable to the creation of protecting groups and theirremoval can be found in T. W. Greene, Protecting Groups in OrganicSynthesis, 3rd edition, John Wiley & Sons, Inc. 1999.

Compounds according to the present invention may be convenientlyprepared, or formed during the process of the invention, as solvates(e.g., hydrates). Hydrates of compounds of the present invention may beconveniently prepared by recrystallization from an aqueous/organicsolvent mixture, using organic solvents such as dioxin, tetrahydrofuranor methanol.

Compounds according to the present invention can also be prepared astheir individual stereoisomers by reacting a racemic mixture of thecompound with an optically active resolving agent to form a pair ofdiastereoisomeric compounds, separating the diastereomers and recoveringthe optically pure enantiomer. While resolution of enantiomers can becarried out using covalent diastereomeric derivatives of compounds,dissociable complexes are preferred (e.g., crystalline diastereoisomericsalts). Diastereomers have distinct physical properties (e.g., meltingpoints, boiling points, solubilities, reactivity, etc.) and can bereadily separated by taking advantage of these dissimilarities. Thediastereomers can be separated by chromatography or, preferably, byseparation/resolution techniques based upon differences in solubility.The optically pure enantiomer is then recovered, along with theresolving agent, by any practical means that would not result inracemization. A more detailed description of the techniques applicableto the resolution of stereoisomers of compounds from their racemicmixture can be found in Jean Jacques Andre Collet, Samuel H. Wilen,Enantiomers, Racemates and Resolutions, John Wiley & Sons, Inc. (1981).

As used herein the symbols and conventions used in these processes,schemes and examples are consistent with those used in the contemporaryscientific literature, for example, the Journal of the American ChemicalSociety or the Journal of Biological Chemistry. Standard single-letteror thee-letter abbreviations are generally used to designate amino acidresidues, which are assumed to be in the L-configuration unlessotherwise noted. Unless otherwise noted, all starting materials wereobtained from commercial suppliers and used without furtherpurification. Specifically, the following abbreviations may be used inthe examples and throughout the specification: μL (microliters) Ac(acetyl) atm (atmosphere) ATP (Adenosine Triphophatase) BOC(tert-butyloxycarbonyl) BOP (bis(2-oxo-3-oxazolidinyl)phosphinicchloride) BSA (Bovine Serum Albumin) CBZ (benzyloxycarbonyl) CDI(1,1-carbonyldiimidazole) DCC (dicyclohexylcarbodiimide) DCE(dichloroethane) DCM (dichloromethane) DMAP (4-dimethylaminopyridine)DME (1,2-dimethoxyethane) DMF (N,N-dimethylformamide) DMPU(N,N′-dimethylpropyleneurea) DMSO (dimethylsulfoxide) EDCI(ethylcarbodiimide hydrochloride) EDTA (Ethylenediaminetetraacetic acid)Et (ethyl) Et₂O (diethyl ether) EtOAc (ethyl acetate) FMOC(9-fluorenylmethoxycarbonyl) g (grams) h (hours) HOAc or AcOH (aceticacid) HOBT (1-hydroxybenzotriazole) HOSu (N-hydroxysuccinimide) HPLC(high pressure liquid chromatography) Hz (Hertz) i.v. (intravenous) IBCF(isobutyl chloroformate) i-PrOH (isopropanol) L (liters) M (molar) mCPBA(meta-chloroperbenzoic acid) Me (methyl) MeOH (methanol) mg (milligrams)MHz (megahertz) min (minutes) mL (milliliters) mM (millimolar) mmol(millimoles) mol (moles) MOPS (Morpholinepropanesulfonic acid) mp(melting point) NaOAc (sodium acetate) OMe (methoxy) psi (pounds persquare inch) RP (reverse phase) RT (ambient temperature) SPA(Scintillation Proximity Assay) TBAF (tetra-n-butylammonium fluoride)TBS (t-butyldimethylsilyl) tBu (tert-butyl) TEA (triethylamine) TFA(trifluoroacetic acid) TFAA (trifluoroacetic anhydride) THF(tetrahydrofuran) TIPS (triisopropylsilyl) TLC (thin layerchromatography) TMS (trimethylsilyl) TMSE (2-(trimethylsilyl)ethyl) Tr(retention time)

All references to ether or Et2O are to diethyl ether; and brine refersto a saturated aqueous solution of NaCl. Unless otherwise indicated, alltemperatures are expressed in ° C. (degrees Centigrade). All reactionsare conducted under an inert atmosphere at RT unless otherwise noted.

1H NMR spectra were recorded on a Bruker Avance 400. Chemical shifts areexpressed in parts per million (ppm). Coupling constants are in units ofHertz (Hz). Splitting patterns describe apparent multiplicities and aredesignated as s (singlet), d (doublet), t (triplet), q (quartet), m(multiplet), br (broad).

Low-resolution mass spectra (MS) and compound purity data were acquiredon a Waters ZQ LC/MS single quadrupole system equipped with electrosprayionization (ESI) source, UV detector (220 and 254 nm), and evaporativelight scattering detector (ELSD). Thin-layer chromatography wasperformed on 0.25 mm E. Merck silica gel plates (60F-254), visualizedwith UV light, 5% ethanolic phosphomolybdic acid, Ninhydrin orp-anisaldehyde solution. Flash column chromatography was performed onsilica gel (230-400 mesh, Merck).

The starting materials and reagents used in preparing these compoundsare either available from commercial suppliers such as the AldrichChemical Company (Milwaukee, Wisc.), Bachem (Torrance, Calif.), Sigma(St. Louis, Mo.), or may be prepared by methods well known to a personof ordinary skill in the art, following procedures described in suchstandard references as Fieser and Fieser's Reagents for OrganicSynthesis, vols. 1-17, John Wiley and Sons, New York, N.Y., 1991; Rodd'sChemistry of Carbon Compounds, vols. 1-5 and supps., Elsevier SciencePublishers, 1989; Organic Reactions, vols. 1-40, John Wiley and Sons,New York, N.Y., 1991; March J.: Advanced Organic Chemistry, 4th ed.,John Wiley and Sons, New York, N.Y.; and Larock: Comprehensive OrganicTransformations, VCH Publishers, New York, 1989.

The entire disclosure of all documents cited throughout this applicationare incorporated herein by reference.

Synthetic Schemes For Compounds of the Present Invention

Compounds according to the present invention may be synthesizedaccording to the reaction schemes shown below. Other reaction schemescould be readily devised by those skilled in the art. It should also beappreciated that a variety of different solvents, temperatures and otherreaction conditions can be varied to optimize the yields of thereactions.

In the reactions described hereinafter it may be necessary to protectreactive functional groups, for example hydroxy, amino, imino, thio orcarboxy groups, where these are desired in the final product, to avoidtheir unwanted participation in the reactions. Conventional protectinggroups may be used in accordance with standard practice, for examplessee T. W. Greene and P. G. M. Wuts in “Protective Groups in OrganicChemistry” John Wiley and Sons, 1991.

General synthetic routes for producing compounds of the presentinvention are shown in the schemes below.

A solution of B (0.5 mmol) in DMF (2.5 mL) is treated with anappropriate heterocycle A (0.5 mmol) and solid K₂CO₃ (0.6 mmol). Afterstirring at 23° C. for 18 h, the reaction is poured into water (10 mL)and the resulting solid isolated by filtration. The filter cake can berinsed with water and allowed to dry in vacuo to yield a mixture ofregioisomeric alkylation products C, D and E, which can be separated byflash chromatography. If no solid is formed, the DMF/water mixture canbe extracted with ethylacetate. The combined extracts can be dried(MgSO₄), concentrated in vacuo and purified by flash chromatography.

A solution of the alkylation products C, D and/or E (0.25 mmol) indioxane (1 mL) is treated with aqueous LiOH (1 M, 1.0 mL). Afterstirring at 23° C. for 2 h, the reaction is neutralized with aqueous HCl(1 M, 2.0 mL) and the resulting solid isolated by filtration. The filtercake can be rinsed with water and allowed to dry in vacuo to yield thecorresponding carboxylic acid.

A solution of the carboxylic acid formed above (0.1 mmol) in DMF (1 mL)is sequentially treated with EDC (0.12 mmol), HOBt (0.12 mmol), asubstituted or unsubstituted 1,2-phenylenediamine (0.12 mmol) and NMM(0.3 mmol). After stirring at 23° C. for 4 h, the reaction is pouredinto water (10 mL) and the resulting solid isolated by filtration. Thefilter cake can be rinsed with water and allowed to dry in vacuo toyield the corresponding amide F, G and/or H.

In relation to Scheme 2, the alkylation of I with B, hydrolysis of Jand/or K, and coupling with the 1,2-phenylenediamine to provide L and/orM proceed as described in Scheme

In relation to Scheme 3, nitrobenzenes J′ and K′ may be prepared asdescribed in connection with Schemes 1 and 2.

A solution of the nitrobenzene (J′ and/or K′) (1.0 mmol) in MeOH (10 mL)with Pd/C (10 wt %, 50 mg) is stirred vigorously under hydrogen for 4 h.The reaction is filtered and concentrated in vacuo to give thecorresponding aniline that can be carried forward.

A solution of the aniline (1.0 mmol) in dichloromethane (10 mL) istreated sequentially with the appropriate acid chloride or chloroformate(R(CO)Cl, wherein R is, for example, an optionally substituted alkoxy,alkyl, heterocycloalkyl or aryl) (1.1 mmol) and triethylamine (2.2mmol). After stirring at 23° C. for 4 h, the reaction is concentrated invacuo to yield the corresponding acylation product (N and/or O). Ifnecessary, purification can be carried out by flash chromatography orrecrystallization.

Compounds N and/or O can be coupled with a substituted or unsubstituted1,2-phenylenediamine to yield P and/or Q, as described in connectionwith Schemes 1 and 2.

Chiral components can be separated and purified using any of a varietyof techniques known to those skilled in the art. For example, chiralcomponents can be purified using supercritical fluid chromatography(SFC). In one particular variation, chiral analytical SFC/MS analysesare conducted using a Berger analytical SFC system (AutoChem, Newark,Del.) which consists of a Berger SFC dual pump fluid control module witha Berger FCM 1100/1200 supercritical fluid pump and FCM 1200 modifierfluid pump, a Berger TCM 2000 oven, and an Alcott 718 autosampler. Theintegrated system can be controlled by BI-SFC Chemstation softwareversion 3.4. Detection can be accomplished with a Watrers ZQ 2000detector operated in positive mode with an ESI interface and a scanrange from 200-800 Da with 0.5 second per scan. Chromatographicseparations can be performed on a ChiralPak AD-H, ChiralPak AS-H,ChiralCel OD-H, or ChiralCel OJ-H column (5μ, 4.6×250 mm; ChiralTechnologies, Inc. West Chester, Pa.) with 10 to 40% methanol as themodifier and with or without ammonium acetate (10 mM). Any of a varietyof flow rates can be utilized including, for example, 1.5 or 3.5 mL/minwith an inlet pressure set at 100 bar. Additionally, a variety of sampleinjection conditions can be used including, for example, sampleinjections of either 5 or 10 μL in methanol at 0.1 mg/mL inconcentration.

In another variation, preparative chiral separations are performed usinga Berger MultiGram II SFC purification system. For example, samples canbe loaded onto a ChiralPak AD column (21×250 mm, 10μ). In particularvariations, the flow rate for separation can be 70 mL/min, the injectionvolume up to 2 mL, and the inlet pressure set at 130 bar. Stackedinjections can be applied to increase the efficiency.

In each of the above reaction procedures or schemes, the varioussubstituents may be selected from among the various substituentsotherwise taught herein.

Descriptions of the syntheses of particular compounds according to thepresent invention based on the above reaction scheme are set forthherein.

Examples of HDAC Inhibitors

The present invention is further exemplified, but not limited by, thefollowing examples that describe the synthesis of particular compoundsaccording to the invention.

Examples 1 and 2 4-((1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamideand 4-((2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide

The title compounds were prepared using the procedure described inScheme 2. In particular, a solution of methyl 4-bromomethylbenzoate (0.5mmol) in DMF (2.5 mL) was treated with the indazole (0.5 mmol) and solidK₂CO₃ (0.6 mmol). After stirring at 23° C. for 18 h, the reaction waspoured into water (10 mL) and the resulting solid was isolated byfiltration. The filter cake was rinsed with water and allowed to dry invacuo to yield a mixture of regioisomeric alkylation products, whichwere separated by flash chromatography.

A solution of the methyl ester (0.25 mmol) in dioxane (1 mL) was treatedwith aqueous LiOH (1 M, 1.0 mL). After stirring at 23° C. for 2 h, thereaction was neutralized with aqueous HCl (1 M, 2.0 mL) and theresulting solid was isolated by filtration. The filter cake was rinsedwith water and allowed to dry in vacuo to yield the correspondingbenzoic acid.

A solution of the appropriate benzoic acid (0.1 mmol) in DMF (1 mL) wassequentially treated with EDC (0.12 mmol), HOBt (0.12 mmol),1,2-phenylenediame (0.12 mmol) and NMM (0.3 mmol). After stirring at 23°C. for 4 h, the reaction was poured into water (10 mL) and the resultingsolid was isolated by filtration. The filter cake was rinsed with waterand allowed to dry in vacuo to yield the corresponding amide.

Example 1: ¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.85 (s, 2 H) 5.74 (s, 2 H)6.53-6.58 (m, 1 H) 6.73 (dd, J=7.83, 1.26 Hz, 1 H) 6.91-6.96 (m, 1 H)7.09-7.16 (m, 2 H), 7.28-7.39 (m, 3 H) 7.70 (d, J=8.34 Hz, 1 H) 7.77 (d,J=8.34 Hz, 1 H) 7.87 (d, J=8.08 Hz, 2 H) 8.13 (s, 1 H) 9.56 (s, 1 H).ESI-MS: m/z 343.4 (M+H)⁺.

Example 2: ¹H NMR (400 MHz, DMSO-D6) δ ppm 4.94 (s, 2 H) 5.72 (s, 2 H)6.57 (t, J=7.58 Hz, 1 H) 6.74-6.77 (m, 1 H) 6.95 (td, J=7.58, 1.52 Hz, 1H) 7.00-7.05 (m, 1 H) 7.13 (d, J=7.58 Hz, 1 H) 7.22 (dd, J=8.21, 7.20Hz, 1 H) 7.41 (d, J=8.08 Hz, 2 H) 7.58 (d, J=8.59 Hz, 1 H) 7.71 (d,J=8.59 Hz, 1 H) 7.93 (d, J=8.08 Hz, 2 H) 8.51 (s, 1 H) 9.62 (s, 1 H).ESI-MS: m/z 343.4 (M+H)⁺.

Examples 3 and 44-((5-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide and4-((5-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide

The title compounds were prepared using a procedure analogous to thatdescribed in Examples 1 and 2 except that the nitrobenzene was reducedand the aniline acylated as further described in Scheme 2. Specifically,the alkylation with methyl 4-bromomethylbenzoate, hydrolysis of methylbenzoate, and coupling with 1,2-phenylenediamine proceed as described inconnection with Examples 1 and 2. A solution of the nitrobenzene (1.0mmol) in MeOH (10 mL) with Pd/C (10 wt %, 50 mg) was then stirredvigorously under hydrogen for 4 h. The reaction was filtered andconcentrated in vacuo to give the corresponding aniline that was carriedforward. A solution of the aniline (1.0 mmol) in dichloromethane (10 mL)was treated sequentially with the appropriate acid chloride orchloroformate (1.1 mmol) and triethylamine (2.2 mmol). After stirring at23° C. for 4 h, the reaction was concentrated in vacuo to yield thecorresponding acylation product. If necessary, purification can becarried out by flash chromatography or recrystallization.

Example 3: ¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.02 (s, 3 H) 4.85 (s, 2 H)5.69 (s, 2 H) 6.49-6.60 (m, 1 H) 6.73 (d, J=8.08 Hz, 1 H) 6.87-6.99 (m,2 H) 7.11 (d, J=8.08 Hz, 1 H) 7.29 (d, J=8.08 Hz, 2 H) 7.39 (dd, J=9.09,1.77 Hz, 1 H) 7.61 (d, J=8.84 Hz, 1 H) 7.87 (d, J=8.08 Hz, 2 H) 8.06 (s,1 H) 8.12 (s, 1 H) 9.56 (s, 1 H). ESI-MS: m/z 400.5 (M+H)⁺.

Example 4: ¹H NMR (400 MHz, DMSO-D6) δ ppm 2.03 (s, 3 H) 4.87 (s, 2 H)5.67 (s, 2 H) 6.45-6.65 (m, 1 H) 6.74 (d, J=8.08 Hz, 1 H) 6.86-7.02 (m,1 H) 7.13 (d, J=7.33 Hz, 1 H) 7.20 (dd, J=9.35, 1.77 Hz, 1 H) 7.39 (d,J=8.08 Hz, 2 H) 7.52 (d, J=9.09 Hz, 1 H) 7.92 (d, J=8.08 Hz, 2 H) 8.12(s, 1 H) 8.41 (s, 1 H) 9.61 (s, 1 H) 9.85 (s, 1 H). ESI-MS: m/z 400.5(M+H)⁺.

Example 5 N-(2-aminophenyl)-4-((5-nitro-1H-indazol-1-yl)methyl)benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 1 and 2. ¹H NMR (400 MHz, DMSO-D6) of thetrifluoroacetic acid salt: δ ppm 5.86 (s, 2 H) 6.96 (s, 1 H) 7.05 (d,J=7.58 Hz, 1 H) 7.13 (d, J=7.33 Hz, 1 H) 7.25 (d, J=7.83 Hz, 1 H) 7.37(d, J=8.08 Hz, 2 H) 7.92 (d, J=8.34 Hz, 2 H) 7.96 (d, J=9.09 Hz, 1 H)8.24 (dd, J=9.35, 2.27 Hz, 1 H) 8.47 (s, 1 H) 8.85 (d, J=2.02 Hz, 1 H)9.99 (s, 1 H). ESI-MS: m/z 388.4 (M+H)⁺.

Example 64-((5-benzamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) δ ppm 4.86 (s,2 H) 5.73 (s, 2 H) 6.49-6.62 (m, 1 H) 6.73 (d, J=7.83 Hz, 1 H) 6.85-6.97(m, 1 H) 7.11 (d, J=7.83 Hz, 1 H) 7.30 (d, J=8.08 Hz, 2 H) 7.45-7.62 (m,3 H) 7.61-7.74 (m, 2 H) 7.88 (d, J=8.34 Hz, 2 H) 7.96 (d, J=6.82 Hz, 2H) 8.12 (s, 1 H) 8.26 (s, 1 H) 9.57 (s, 1 H) 10.28 (s, 1 H). ESI-MS: m/z462.5 (M+H)⁺.

Example 7 4-((5-amino-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) δ ppm 4.85 (bs,4 H) 5.59 (s, 2 H) 6.55 (s, 1 H) 6.71-6.80 (m,3 H) 6.93 (d, J=6.32 Hz, 1H) 7.11 (d, J=6.82 Hz, 1 H) 7.26 (d, J=7.58 Hz, 2 H) 7.30-7.40 (m, 1 H)7.73-7.83 (m, 1 H) 7.86 (d, J=7.58 Hz, 2 H) 9.56 (s, 1 H). ESI-MS: m/z358.4 (M+H)⁺.

Example 8 N-(2-aminophenyl)-4-((5-nitro-2H-indazol-2-yl)methyl)benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 1 and 2. ¹H NMR (400 MHz, DMSO-D6) δ ppm 4.87 (br.s., 2 H) 5.75-5.88 (m, 2 H) 6.51-6.61 (m, 1 H) 6.74 (d, J=7.33 Hz, 1 H)6.90-6.98 (m, 1 H) 7.13 (d, J=7.58 Hz, 1 H) 7.46 (d, J=8.08 Hz, 2 H)7.77 (d, J=9.60 Hz, 1 H) 7.94 (d, J=8.08 Hz, 2 H) 7.97-8.04 (m, 1 H)8.91 (d, 1 H) 8.94-9.01 (m, 1 H) 9.62 (s, 1 H). ESI-MS: m/z 388.4(M+H)⁺.

Example 9 4-((5-amino-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) of thetrifluoroacetic acid salt: δ ppm 5.76 (s, 2 H) 6.84-6.95 (m, 1 H) 7.01(d, J=7.83 Hz, 1 H) 7.08-7.20 (m, 2 H) 7.24 (s, 1 H) 7.44 (d, J=8.08 Hz,2 H) 7.69-7.79 (m, 2 H) 7.96 (d, J=7.83 Hz, 2 H) 8.64 (s, 1 H) 9.96 (s,1 H). ESI-MS: m/z 358.4 (M+H)⁺.

Example 104-((5-benzamido-2H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) δ ppm 4.87 (s,2 H) 5.61-5.76 (s, 2 H) 6.56 (t, J=7.33 Hz, 1 H) 6.75 (d, J=8.08 Hz, 1H) 6.88-7.00 (m, 1 H) 7.13 (d, J=8.08 Hz, 1 H) 7.41 (d, J=7.07 Hz, 2 H)7.45-7.63 (m, 3 H) 7.83-8.02 (m, 4 H) 8.26 (s, 1 H) 8.49 (s, 1 H) 9.61(s, 1 H) 10.20 (s, 1 H). ESI-MS: m/z 462.5 (M+H)⁺.

Example 11 2-Methoxyethyl2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) δ ppm 3.52-3.60(m, 2 H) 4.13-4.22 (m, 2 H) 4.86 (bs, 2 H) 5.66 (s, 2 H) 6.56 (m, 1 H)6.75 (m, 1 H) 6.93 (d, J=6.82 Hz, 1 H) 7.13 (m, 1 H) 7.21 (d, J=2.02 Hz,1 H) 7.39 (d, J=7.83 Hz, 2 H) 7.52 (s, 1 H) 7.82-7.89 (m, 2 H) 7.91 (s,1 H) 8.40 (s, 1 H) 9.60 (s, 1 H) 9.64 (s, 1 H). ESI-MS: m/z 460.5(M+H)⁺.

Example 12 Methyl2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) δ ppm 3.32 (s,3 H) 4.87 (s, 2 H) 5.58-5.73 (m, 2 H) 6.48-6.62 (m, 1 H) 6.74 (d, J=8.08Hz, 1 H) 6.88-7.00 (m, 1 H) 7.07-7.17 (m, 1 H) 7.18-7.24 (m, 1 H) 7.39(dd, J=8.08, 4.55 Hz, 2 H) 7.46-7.57 (m, 1 H) 7.88-8.00 (m, 2 H) 8.39(d, J=6.32 Hz, 1 H) 8.56 (s, 1 H) 9.54 (s, 1 H) 9.61 (s, 1 H). ESI-MS:m/z 416.5 (M+H)⁺.

Example 13 2-Methoxyethyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) δ ppm 3.31 (s,3 H) 3.47-3.61 (m, 2H) 4.12-4.23 (m, 2 H) 4.85 (s, 2 H) 5.69 (s, 2 H)6.55 (t, J=7.58 Hz, 1 H) 6.69-6.78 (m, 1 H) 6.86-7.01 (m, 1 H) 7.11 (d,J=7.83 Hz, 1 H) 7.28 (d, J=8.34 Hz, 2 H) 7.33-7.45 (m, 1 H) 7.61 (d,J=9.09 Hz, 1 H) 7.87 (m, 3 H) 8.05 (s, 1 H) 9.56 (s, 1 H) 9.71 (s, 1 H).ESI-MS: m/z 460.5 (M+H)⁺.

Example 14 Methyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) of thetrifluoroacetic acid salt: δ ppm 3.65 (s, 3 H) 5.70 (s, 2 H) 6.90 (s, 1H) 6.99 (s, 1 H) 7.11 (s, 1 H) 7.23 (d, J=7.83 Hz, 1 H) 7.31 (d, J=8.08Hz, 2 H) 7.38 (s, 1 H) 7.61 (d, J=9.09 Hz, 1 H) 7.89 (d, J=7.83 Hz, 3 H)8.06 (s, 1 H) 9.61 (s, 1 H) 9.91 (s, 1 H). ESI-MS: m/z 416.5 (M+H)⁺.

Example 15 Benzyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) of thetrifluoroacetic acid salt: δ ppm 4.85 (s, 2 H) 5.14 (s, 2 H) 5.69 (s, 2H) 6.55 (s, 1 H) 6.73 (d, J=8.08 Hz, 1 H) 6.93 (s, 1 H) 7.04-7.18 (m, 1H) 7.22-7.49 (m, 7 H) 7.61 (s, 1 H) 7.79-8.00 (m, 4 H) 8.05 (s, 1 H)9.56 (s, 1 H) 9.74 (s, 1 H). ESI-MS: m/z 492.5 (M+H)⁺.

Example 16 Benzyl2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) of thetrifluoroacetic acid salt: δ ppm 5.14 (s, 2 H) 5.68 (s, 2 H) 6.81-6.94(m, 1 H) 6.95-7.05 (m, 1 H) 7.10 (s, 1 H) 7.22 (dd, J=9.35, 1.77 Hz, 2H) 7.29-7.47 (m, 7 H) 7.51 (d, J=9.35 Hz, 2 H) 7.94 (d, J=8.08 Hz, 2 H)8.41 (s, 1 H) 9.68 (s, 1 H) 9.94 (s, 1 H). ESI-MS: m/z 492.5 (M+H)⁺.

Example 17N-(4-Amino-biphenyl-3-yl)-4-(5-nitro-indazol-2-ylmethyl)-benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) of thetrifluoroacetic acid salt: δ ppm 5.84 (s, 2 H) 6.97 (s, 1 H) 7.25 (s, 1H) 7.39 (s, 3 H) 7.44-7.62 (m, 5 H) 7.79 (s, 1 H) 7.99 (s, 3 H) 8.98 (s,2 H) 9.89 (s, 1 H). ESI-MS: m/z 464.5 (M+H)⁺.

Example 18N-(2-(4-((2-Aminophenyl)carbamoyl)benzyl)-2H-indazol-5-yl)morpholine-4-carboxamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) of thetrifluoroacetic acid salt: δ ppm 3.34-3.45 (m, 4 H) 3.59 (m, 4 H) 4.86(s, 2 H) 5.66 (s, 2 H) 6.75 (m, 1 H) 6.86-6.98 (m, 1 H) 7.06-7.16 (m, 1H) 7.20-7.30 (m, 1 H) 7.38 (d, 2 H) 7.46 (m, 1 H) 7.78 (s, 1 H) 7.91 (d,2 H) 8.36 (s, 1 H) 8.40-8.48 (m, 1 H) 9.61 (s, 1 H). ESI-MS: m/z 471.5(M+H)⁺.

Example 195-((2H-Indazol-2-yl)methyl)-N-(2-aminophenyl)thiophene-2-carboxamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 1 and 2. ¹H NMR (400 MHz, DMSO-D6) δ ppm 4.88 (s,2 H) 5.89 (s, 2 H) 6.54-6.60 (m, 1 H) 6.75 (d, J=8.08 Hz, 1 H) 6.94-6.99(m, 1 H) 7.02-7.10 (m, 2 H) 7.22-7.30 (m, 2 H) 7.62 (d, J=8.84 Hz, 1 H)7.72 (d, J=8.59 Hz, 1 H) 7.83 (d, J=3.03 Hz, 1 H) 8.51 (s, 1 H) 9.68 (s,1 H). ESI-MS: m/z 349.4 (M+H)⁺.

Example 20N-(2-Aminophenyl)-5-((5-nitro-2H-indazol-2-yl)methyl)thiophene-2-carboxamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 1 and 2. ¹H NMR (400 MHz, DMSO-D6) δ ppm 4.89 (s,2 H) 6.01 (s, 2 H) 6.55-6.59 (m, 1 H) 6.75 (d, J=8.08 Hz, 1 H) 6.95 (d,J=7.83 Hz, 1H) 7.07 (d, J=7.83 Hz, 1 H) 7.30 (s, 1 H) 7.82 (d, J=9.35Hz, 2 H) 8.01-8.05 (m, 1 H) 8.93-8.97 (m, 2 H) 9.70 (s, 1 H). ESI-MS:m/z 394.4 (M+H)⁺.

Example 21N-(1-(4-((2-Aminophenyl)carbamoyl)benzyl)-1H-indazol-5-yl)morpholine-4-carboxamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) δ ppm 3.37-3.47(m, 4 H) 3.50-3.66 (m, 4 H) 5.62 (s, 2 H) 6.56 (m, 1 H) 6.74 (d, J=8.59Hz, 1 H) 6.94 (m, 1 H) 7.11 (m, 1 H) 7.29 (d, J=8.08 Hz, 2 H) 7.39 (dd,J=9.09, 1.77 Hz, 1 H) 7.57 (d, J=9.09 Hz, 1 H) 7.74-7.89 (m, 3 H)7.96-8.05 (m, 1 H) 8.52 (s, 1 H) 9.57 (s, 1 H). ESI-MS: m/z 471.5(M+H)⁺.

Example 22 2-Morpholinoethyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) δ ppm 2.41 (m,2 H) 2.56 (m, 2 H) 3.55 (m, 4 H) 4.18 (m, 4 H) 4.85 (s, 2 H) 5.68 (s, 2H) 6.47-6.63 (m, 1 H) 6.73 (d, J=8.08 Hz, 1 H) 6.85-6.99 (m, 1 H) 7.10(s, 1 H) 7.28 (d, J=8.34 Hz, 2 H) 7.39 (d, J=8.84 Hz, 1 H) 7.61 (d,J=9.09 Hz, 1 H) 7.87 (d, J=8.08 Hz, 3 H) 8.04 (s, 1 H) 9.55 (s, 1 H)9.60-9.71 (m, 1 H). ESI-MS: m/z 515.6 (M+H)⁺.

Example 23 Pyridin-3-ylmethyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate

The title compound was prepared using a procedure analogous to thatdescribed in Examples 3 and 4. ¹H NMR (400 MHz, DMSO-D6) δ ppm 4.85 (bs,2 H) 5.18 (s, 2 H) 5.69 (s, 2 H) 6.48-6.59 (m, 1 H) 6.73 (dd, J=8.08,1.26 Hz, 1 H) 6.87-6.98 (m, 1 H) 7.11 (d, J=7.33 Hz, 1 H) 7.28 (d,J=8.34 Hz, 2 H) 7.34-7.47 (m, 2 H) 7.62 (d, J=9.09 Hz, 2 H) 7.77-7.94(m, 3 H) 8.03-8.08 (m, 1 H) 8.54 (dd, J=4.80, 1.52 Hz, 1 H) 8.65 (d,J=1.77 Hz, 1 H) 9.56 (s, 1 H) 9.78 (s, 1 H). ESI-MS: m/z 493.5 (M+H)⁺.

Example 245-((1H-Indazol-1-yl)methyl)-N-(2-aminophenyl)thiophene-2-carboxamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 1 and 2. ¹H NMR (400 MHz, DMSO-D6) δ ppm 4.86 (s,2 H) 5.90 (s, 2 H) 6.52-6.59 (m, 1 H) 6.74 (d, J=7.33 Hz, 1 H) 6.91-6.99(m, 1 H) 7.05 (d, J=7.33 Hz, 1 H) 7.13-7.23 (m, 2 H) 7.42 (s, 1 H) 7.79(m, 3 H) 8.15 (s, 1 H) 9.62 (s, 1 H). ESI-MS: m/z 349.4 (M+H)⁺.

Example 254-((2H-Pyrazolo[3,4-b]pyridin-2-yl)methyl)-N-(2-aminophenyl)benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 1 and 2. ¹H NMR (400 MHz, DMSO-D6) of thebis-trifluoroacetic acid salt: δ ppm 6.11 (s, 2 H) 6.79 (d, J=8.08 Hz, 1H) 6.92 (d, J=8.08 Hz, 1 H) 7.02-7.10 (m, 1 H) 7.19 (d, J=7.58 Hz, 1 H)7.63 (d, J=8.08 Hz, 2H) 7.79 (dd, J=8.08, 5.81 Hz, 1 H) 7.97 (d, J=8.34Hz, 2 H) 9.11-9.19 (m, 1 H) 9.23 (d, J=7.83 Hz, 1 H) 9.40 (d, J=4.80 Hz,1 H) 9.86 (s, 1 H). ESI-MS: m/z 344.4 (M+H)⁺.

Example 26N-(4-Amino-biphenyl-3-yl)-4-pyrazolo[3,4-b]pyridin-2-ylmethyl-benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 1 and 2. ¹H NMR (400 MHz, DMSO-D6) of thebis-trifluoroacetic acid salt: δ ppm 6.11 (s, 2H) 6.91 (d, J=8.34 Hz, 1H) 7.24 (t, J=7.33 Hz, 1 H) 7.33-7.41 (m, 3 H) 7.48-7.56 (m, 3 H) 7.64(d, J=8.34 Hz, 2 H) 7.79 (dd, J=8.08, 5.81 Hz, 1 H) 8.00 (d, J=8.34 Hz,2 H) 9.16 (br. s., 1 H) 9.23 (d, J=7.83 Hz, 1 H) 9.35-9.45 (m, 1 H) 9.82(s, 1 H). ESI-MS: m/z (M+H)⁺.

Example 27 N-(4-Amino-biphenyl-3-yl)-4-indazol-2-ylmethyl-benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 1 and 2. ¹H NMR (400 MHz, DMSO-D6) of thetrifluoroacetic acid salt: δ ppm 5.74 (s, 2 H) 6.98-7.06 (m, 1 H) 7.08(d, J=8.34 Hz, 1 H) 7.18-7.25 (m, 1 H) 7.28 (t, 1 H) 7.35-7.48 (m, 5 H)7.58 (m, 4 H) 7.71 (d, J=8.34 Hz, 1 H) 7.98 (d, J=8.08 Hz, 2 H) 8.53 (s,1 H) 10.02 (s, 1 H). ESI-MS: m/z 419.5 (M+H)⁺.

Example 28N-(2-Aminophenyl)-4-((3-methyl-1H-indazol-1-yl)methyl)benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 1 and 2. ¹H NMR (400 MHz, DMSO-D6) δ ppm 2.48 (s,3 H) 4.87 (s, 2 H) 5.66 (s, 2 H) 6.54-6.61 (m, 1 H) 6.76 (dd, J=7.83,1.26 Hz, 1 H) 6.91-6.99 (m, 1 H) 7.09-7.17 (m, 2 H) 7.31 (d, J=8.34 Hz,2 H) 7.34-7.40 (m, 1 H) 7.64 (d, J=8.34 Hz, 1 H) 7.73 (d, J=8.08 Hz, 1H) 7.89 (d, J=8.34 Hz, 2 H) 9.57 (s, 1 H). ESI-MS: m/z 357.4 (M+H)⁺.

Example 29N-(2-Aminophenyl)-4-((3-methyl-2H-indazol-2-yl)methyl)benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 1 and 2. ¹H NMR (400 MHz, DMSO-D6) δ ppm 2.61 (s,3 H) 4.88 (s, 2 H) 5.72 (s, 2 H) 6.50-6.64 (m, 1 H) 6.72-6.82 (m, 1 H)6.93-7.03 (m, 2 H) 7.12-7.17 (m, 1 H) 7.20-7.31 (m, 3 H) 7.55 (d, J=8.59Hz, 1 H) 7.68 (d, J=8.59 Hz, 1 H) 7.93 (d, J=8.08 Hz, 2 H) 9.62 (s, 1H). ESI-MS: m/z 357.4 (M+H)⁺.

Example 30 4-((1H-indazol-3-ylamino)methyl)-N-(2-aminophenyl)benzamide

The title compound was prepared using a procedure analogous to thatdescribed in Examples 1 and 2. ¹H NMR (400 MHz, DMSO-D6) δ ppm 4.56 (d,J=6.15 Hz, 2 H) 4.88 (s, 2 H) 6.49-6.63 (m, 1 H) 6.63-6.73 (m, 1 H) 6.77(d, J=7.98 Hz, 1 H) 6.84-7.01 (m, 2 H) 7.16 (d, J=7.48 Hz, 1 H)7.20-7.29 (m, 2 H) 7.52 (d, J=8.14 Hz, 2 H) 7.77 (d, J=8.14 Hz, 1 H)7.92 (d, J=8.14 Hz, 2 H) 9.60 (s, 1 H) 11.40 (s, 1 H). ESI-MS: m/z 358.4(M+H)⁺.

Example 31 4-((1H-pyrazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (499 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 5.38(s, 2 H), 6.25-6.33 (m, 2 H), 7.18-7.26 (m, 3 H), 7.31-7.38 (m, 3 H),7.46-7.53 (m, 1 H), 7.84-7.89 (m, 1 H), 7.92-7.99 (m, 1 H), 10.09 (s, 1H). ESI-MS: m/z 293.3 (M+H)⁺.

Example 32N-(2-(4-((2-Aminophenyl)carbamoyl)benzyl)-2H-indazol-5-yl)morpholine-4-carboxamide

¹H NMR (400 MHz, DMSO-D6) δ ppm 3.36-3.47 (m, 4 H) 3.61 (m, 4 H) 4.85(s, 2 H) 5.69 (s, 2 H) 6.77 (m, 1 H) 6.94 (m, 1 H) 7.12 (m, 1 H) 7.27(m, 1 H) 7.37 (d, 2 H) 7.46 (m, 1 H) 7.78 (s, 1 H) 7.87 (d, 2 H) 8.36(s, 1 H) 8.46 (m, 1 H) 9.56 (s, 1 H). ESI-MS: m/z 471.5 (m+H)⁺.

Example 33 Methyl3-(4-((2H-indazol-2-yl)methyl)benzamido)-4-aminobenzoate

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.73 (s, 14 H), 5.72 (s, 10 H), 5.81 (s,10 H), 6.74 (d, J=8.59 Hz, 6 H), 6.98-7.07 (m, 6 H), 7.17-7.26 (m, 6 H),7.41 (d, J=8.34 Hz, 10 H), 7.51-7.61 (m, 11 H), 7.67-7.77 (m, 11 H),7.94 (d, J=8.08 Hz, 10 H), 8.52 (s, 6 H), 9.60 (s, 1 H). ESI-MS: m/z401.4 (M+H)⁺.

Example 34N-(2-aminophenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.00 (s, 3 H), 4.87 (s, 2 H), 5.29-5.33(m, 2 H), 6.54-6.60 (m, 1 H), 6.73-6.78 (m, 1 H), 6.92-6.97 (m, 1 H),7.13 (d, J=7.58 Hz, 1 H), 7.25-7.30 (m, 3 H), 7.58 (s, 1 H), 7.91 (d,J=8.08 Hz, 2 H), 9.60 (s, 1 H). ESI-MS: m/z 307.4 (M+H)⁺.

Example 35N-(2-aminophenyl)-4-((6-fluoro-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.87 (s, 2 H), 5.70 (s, 2 H), 6.53-6.60(m, 1 H), 6.75 (d, J=8.08 Hz, 1 H), 6.91-6.99 (m, 2 H), 7.13 (d, J=8.08Hz, 1 H), 7.31 (d, J=10.36 Hz, 1 H), 7.41 (d, J=8.08 Hz, 2 H), 7.76-7.83(m, 1 H), 7.93 (d, J=8.08 Hz, 2 H), 8.58 (s, 1 H), 9.61 (s, 1 H).ESI-MS: m/z 361.4 (M+H)⁺.

Example 36N-(2-aminophenyl)-4-((6-fluoro-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.86 (s, 2 H), 5.67-5.72 (m, 2 H),6.53-6.59 (m, 1 H), 6.74 (dd, J=8.08, 1.26 Hz, 1 H), 6.91-6.96 (m, 1 H),6.99-7.06 (m, 1 H), 7.11 (d, J=7.33 Hz, 1 H), 7.33 (d, J=8.08 Hz, 2 H),7.59-7.66 (m, 1 H), 7.81 (dd, J=8.84, 5.31 Hz, 1 H), 7.88 (d, J=8.08 Hz,2 H), 8.13-8.16 (m, 1 H), 9.57 (s, 1 H). ESI-MS: m/z 361.4 (M+H)⁻.

Example 37N-(2-aminophenyl)-4-((5-fluoro-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.86 (s, 2 H), 5.75 (s, 2 H), 6.55 (s, 1H), 6.74 (d, J=7.83 Hz, 1 H), 6.92 (d, J=7.58 Hz, 1 H), 7.10 (s, 1 H),7.23-7.33 (m, 3 H), 7.49-7.59 (m, 1 H), 7.75 (s, 1 H), 7.87 (s, 2 H),8.11 (s, 1 H), 9.57 (s, 1 H). ESI-MS: m/z 361.4 (M+H)⁺.

Example 38N-(2-aminophenyl)-4-((5-fluoro-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.87 (s, 2 H), 5.68 (s, 2 H), 6.52-6.59(m, 1 H), 6.71-6.77 (m, 1 H), 6.91-6.98 (m, 1 H), 7.09-7.17 (m, 2 H),7.37-7.48 (m, 3 H), 7.62-7.68 (m, 1 H), 7.93 (d, J=8.34 Hz, 2 H), 8.50(s, 1 H), 9.60 (s, 1 H). ESI-MS: m/z 361.4 (M+H)⁺.

Example 39 4-(1-(1H-indazol-1-yl)propan-2-yl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 1.20(d, J=6.82 Hz, 3 H), 3.51-3.62 (m, 1 H), 4.54-4.65 (m, 2 H), 6.95 (s, 2H), 7.01-7.13 (m, 3 H), 7.25 (d, J=7.58 Hz, 1 H), 7.29-7.35 (m, 1 H),7.44 (d, J=8.34 Hz, 2 H), 7.65-7.72 (m, 2 H), 7.85 (d, J=8.08 Hz, 2 H),8.02 (s, 1 H), 9.84-10.01 (m, 1 H). ESI-MS: m/z 371.4 (M+H)⁺.

Example 40 4-(2-(1H-indazol-1-yl)ethyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.17-3.28 (m, 2 H), 4.68 (t, J=7.07 Hz,2 H), 4.85 (s, 2 H), 6.51-6.62 (m, 1 H), 6.75 (dd, J=8.08, 1.26 Hz, 1H), 6.88-7.00 (m, 1 H), 7.03-7.18 (m, 2 H), 7.26-7.38 (m, 3 H), 7.62 (d,J=8.34 Hz, 1 H), 7.72 (d, J=8.08 Hz, 1 H), 7.78-7.86 (m, 2 H), 8.04 (s,1 H), 9.56 (s, 1 H). ESI-MS: m/z 357.4 (M+H)⁺.

Example 41 4-(2-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.34 (t, J=7.07 Hz, 2 H), 4.72 (t,J=7.07 Hz, 2 H), 4.85 (s, 2 H), 6.51-6.62 (m, 1 H), 6.74 (dd, J=8.08,1.26 Hz, 1 H), 6.88-7.03 (m, 2 H), 7.11 (d, J=7.33 Hz, 1 H), 7.15-7.25(m, 1 H), 7.29 (d, J=8.08 Hz, 2 H), 7.54-7.68 (m, 2 H), 7.84 (d, J=8.08Hz, 2 H), 8.19-8.30 (m, 1 H), 9.56 (s, 1 H). ESI-MS: m/z 357.4 (M+H)⁺.

Example 42N-(2-aminophenyl)-4-((4-chloro-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.85 (s, 2 H), 5.74-5.81 (m, 2 H),6.52-6.59 (m, 1 H), 6.71-6.77 (m, 1 H), 6.90-6.97 (m, 1 H), 7.11(d,J=7.07 Hz, 1 H), 7.23 (d, J=7.58 Hz, 1 H), 7.31 (d, J=8.34 Hz, 2 H),7.35-7.42 (m, 1 H), 7.74 (d, J=8.59 Hz, 1 H), 7.89 (d, J=8.08 Hz, 2 H),8.18-8.23 (m, 1 H), 9.57 (s, 1 H). ESI-MS: m/z 377.8 (M+H)⁺.

Example 43N-(2-aminophenyl)-4-((4-chloro-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.87 (s, 2 H), 5.70-5.78 (m, 2 H),6.53-6.61 (m, 1 H), 6.75 (dd, J=8.08, 1.26 Hz, 1 H), 6.91-6.98 (m, 1 H),7.13 (d, J=7.07 Hz, 2 H), 7.22 (dd, J=8.59, 7.07 Hz, 1 H), 7.41-7.49 (m,2 H), 7.58 (d, J=8.59 Hz, 1 H), 7.93 (d, J=8.08 Hz, 2 H), 8.67-8.71 (m,1 H), 9.61 (s, 1 H). ESI-MS: m/z 377.8 (M+H)⁺.

Example 44N-(2-aminophenyl)-4-((4,6-difluoro-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.86 (s, 2 H), 5.67-5.75 (m, 2 H),6.52-6.59 (m, 1 H), 6.74 (dd, J=8.08, 1.26 Hz, 1 H), 6.91-6.96 (m, 1 H),7.00-7.07 (m, 1 H), 7.12 (d, J=7.58 Hz, 1 H), 7.34 (d, J=8.08 Hz, 2 H),7.60 (d, J=9.35 Hz, 1 H), 7.89 (d, J=8.08 Hz, 2 H), 8.25-8.30 (m, 1 H),9.58 (s, 1 H). ESI-MS: m/z 379.4 (M+H)⁺.

Example 45N-(2-aminophenyl)-4-((4,6-difluoro-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.87 (s, 2 H), 5.67-5.74 (m, 2 H),6.52-6.61 (m, 1 H), 6.75 (dd, J=7.83, 1.26 Hz, 1 H), 6.88-6.98 (m, 2 H),7.13 (d, J=7.07 Hz, 1 H), 7.25 (d, J=8.84 Hz, 1 H), 7.44 (d, J=8.34 Hz,2 H), 7.93 (d, J=8.08 Hz, 2 H), 8.82 (s, 1 H), 9.61 (s, 1 H). ESI-MS:m/z 379.4 (M+H)⁺.

Example 46N-(2-aminophenyl)-4-((7-fluoro-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.86 (s, 2 H), 5.78 (s, 2 H), 6.51-6.58(m, 1 H), 6.71-6.76 (m, 1 H), 6.89-6.96 (m, 1 H), 7.07-7.14 (m, 2 H),7.17-7.25 (m, 3 H), 7.61 (d, J=7.83 Hz, 1 H), 7.88 (d, J=8.08 Hz, 2 H),8.24 (d, J=2.53 Hz, 1 H), 9.56 (s, 1 H). ESI-MS: m/z 361.4 (M+H)⁺.

Example 47N-(2-aminophenyl)-4-((7-fluoro-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.87 (s, 2 H), 5.72-5.78 (m, 2 H),6.52-6.60 (m, 1 H), 6.75 (dd, J=8.08, 1.26 Hz, 1 H), 6.92-7.04 (m, 3 H),7.13 (d, J=7.33 Hz, 1 H), 7.43 (d, J=8.08 Hz, 2 H), 7.51-7.57 (m, 1 H),7.94 (d, J=8.08 Hz, 2 H), 8.66 (d, J=2.78 Hz, 1 H), 9.62 (s, 1 H).ESI-MS: m/z 361.4 (M+H)⁺.

Example 48N-(2-aminophenyl)-4-((4-fluoro-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d6) □ ppm 4.86 (s, 2 H), 5.77 (s, 2 H), 6.50-6.60(m, 1 H), 6.73 (d, J=8.34 Hz, 1 H), 6.88-6.97 (m, 2 H), 7.11 (d, J=7.58Hz, 1 H), 7.32 (d, J=8.08 Hz, 2 H), 7.34-7.42 (m, 1 H), 7.58 (d, J=8.34Hz, 1 H), 7.89 (d, J=7.83 Hz, 2 H), 8.25 (s, 1 H), 9.57 (s, 1 H).ESI-MS: m/z 361.4 (M+H)⁺.

Example 49N-(2-aminophenyl)-4-((4-fluoro-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.87 (s, 2 H), 5.69-5.75 (m, 2 H),6.52-6.60 (m, 1 H), 6.72-6.82 (m, 2 H), 6.91-6.97 (m, 1 H), 7.12 (d,J=7.33 Hz, 1 H), 7.17-7.24 (m, 1 H), 7.39-7.46 (m, 3 H), 7.93 (d, J=8.08Hz, 2 H), 8.74 (s, 1 H), 9.61 (s, 1 H). ESI-MS: m/z 361.4 (M+H)⁺.

Example 50 (R)-4-(1-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.18 (d, J=7.07 Hz, 4 H), 3.36 (d,J=5.05 Hz, 2 H), 4.29 (q, 1 H), 5.07 (s, 2 H), 6.24 (d, J=7.07 Hz, 1 H),6.76 (s, 1 H), 6.96 (s, 1 H), 7.13 (s, 1 H), 7.24 (d, J=8.59 Hz, 2 H),7.32 (s, 1 H), 7.39-7.44 (m, 1 H), 7.63 (d, J=8.08 Hz, 3 H), 7.80 (d,J=8.84 Hz, 2 H), 7.90 (d, J=8.34 Hz, 1 H), 8.11 (d, J=8.34 Hz, 3 H),8.75 (s, 1 H), 9.79 (s, 1 H). ESI-MS: m/z 357.4 (M+H)⁺.

Example 51 (S)-4-(1-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.18 (d, J=7.07 Hz, 4 H), 3.36 (d,J=5.05 Hz, 2 H), 4.29 (q, 1 H), 5.07 (s, 2 H), 6.24 (d, J=7.07 Hz, 1 H),6.76 (s, 1 H), 6.96 (s, 1 H), 7.13 (s, 1 H), 7.24 (d, J=8.59 Hz, 2 H),7.32 (s, 1 H), 7.39-7.44 (m, 1 H), 7.63 (d, J=8.08 Hz, 3 H), 7.80 (d,J=8.84 Hz, 2 H), 7.90 (d, J=8.34 Hz, 1 H), 8.11 (d, J=8.34 Hz, 3 H),8.75 (s, 1 H), 9.79 (s, 1 H). ESI-MS: m/z 357.4 (M+H)⁺.

Example 52N-(2-aminophenyl)-4-((7-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.51 (s, 3 H), 4.86 (s, 2 H), 5.62-5.71(m, 2 H), 6.51-6.59 (m, 1 H), 6.73 (d, J=7.83 Hz, 1 H), 6.89-6.97 (m, 1H), 7.04-7.14 (m, 2 H), 7.15-7.25 (m, 3 H), 7.56 (d, J=8.08 Hz, 1 H),7.87 (d, J=7.83 Hz, 2 H), 9.56 (s, 1 H). ESI-MS: m/z 375.4 (M+H)⁺.

Example 53N-(2-aminophenyl)-4-((7-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.61 (s, 3 H), 4.87 (s, 2 H), 5.74 (s, 2H), 6.53-6.59 (m, 1 H), 6.74 (dd, J=8.08, 1.26 Hz, 1 H), 6.91-7.02 (m, 3H), 7.12 (d, J=7.58 Hz, 1 H), 7.29 (d, J=8.08 Hz, 2 H), 7.51 (d, J=8.34Hz, 1 H), 7.93 (d, J=8.08 Hz, 2 H), 9.61 (s, 1 H). ESI-MS: m/z 375.4(M+H)⁺.

Example 54N-(2-aminophenyl)-4-((4-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.53-2.58 (m, 3 H), 4.86 (s, 2 H), 5.65(s, 2 H), 6.51-6.59 (m, 1 H), 6.74 (dd, J=7.83, 1.26 Hz, 1 H), 6.84 (dd,J=10.86, 7.58 Hz, 1 H), 6.90-6.97 (m, 1 H), 7.11 (d, J=7.83 Hz, 1 H),7.25-7.36 (m, 3 H), 7.48 (d, J=8.59 Hz, 1 H), 7.88 (d, J=8.08 Hz, 2 H),9.56 (s, 1 H). ESI-MS: m/z 375.4 (M+H)⁺.

Example 55N-(2-aminophenyl)-4-((4-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.65-2.71 (m, 3 H), 4.87 (s, 2 H), 5.71(s, 2 H), 6.53-6.60 (m, 1 H), 6.66-6.77 (m, 2 H), 6.91-6.98 (m, 1 H),7.09-7.19 (m, 2 H), 7.29 (d, J=8.08 Hz, 2 H), 7.36 (d, J=8.59 Hz, 1 H),7.92 (d, J=8.34 Hz, 2 H), 9.61 (s, 1 H), ESI-MS: m/z 375.4 (M+H)⁺.

Example 56N-(2-aminophenyl)-4-((5,6-difluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.45 (s, 3 H), 4.86 (s, 2 H), 5.60 (s, 2H), 6.51-6.60 (m, 1 H), 6.74 (d, J=8.08 Hz, 1 H), 6.89-6.98 (m, 1 H),7.12 (d, J=7.83 Hz, 1 H), 7.32 (d, J=7.83 Hz, 2 H), 7.78-7.84 (m, 1 H),7.85-7.91 (m, 3 H), 9.56 (s, 1 H). ESI-MS: m/z 393.4 (M+H)⁺.

Example 57N-(2-aminophenyl)-4-((5,6-difluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.57 (s, 3 H), 4.98 (s, 1 H), 5.67 (s, 2H), 6.58 (s, 1 H), 6.76 (s, 1 H), 6.95 (s, 1 H), 7.13 (s, 1 H), 7.27 (s,2 H), 7.55 (s, 1 H), 7.75 (s, 1 H), 7.90 (s, 3 H), 9.62 (s, 1 H).ESI-MS: m/z 393.4 (M+H)⁺.

Example 58N-(2-aminophenyl)-4-((6-methoxy-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.31 (s, 3 H), 4.85 (s, 2 H), 5.68(s, 2 H), 6.56 (s, 1 H), 6.72-6.79 (m, 2 H), 6.93 (s, 1 H), 7.11 (s, 1H), 7.20 (s, 1 H), 7.30 (d, J=8.08 Hz, 2 H), 7.61 (s, 1 H), 7.88 (d,J=8.08 Hz, 2 H), 7.98 (s, 1 H), 9.56 (s, 1 H). ESI-MS: m/z 373.4 (M+H)⁺.

Example 59N-(2-aminophenyl)-4-((6-methoxy-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.71-3.79 (m, 3 H), 4.87 (s, 2 H) 5.63(s, 2 H), 6.51-6.62 (m, 1 H), 6.64-6.71 (m, 1 H), 6.72-6.78 (m, 1 H),6.90 (d, J=1.77 Hz, 1 H), 6.91-6.97 (m, 1 H), 7.13 (d, J=7.83 Hz, 1 H),7.38 (d, J=8.34 Hz, 2 H), 7.57 (d, J=9.09 Hz, 1 H), 7.92 (d, J=8.08 Hz,2 H), 8.38 (s, 1 H), 9.60 (s, 1 H). ESI-MS: m/z 373.4 (M+H)⁺.

Example 60N-(2-aminophenyl)-4-((3-chloro-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d6) δ ppm 4.86 (s, 2 H), 5.72 (s, 2 H), 6.52-6.59(m, 1 H), 6.74 (dd, J=8.08, 1.26 Hz, 1 H), 6.90-6.97 (m, 1 H), 7.11 (d,J=6.57 Hz, 1 H), 7.22-7.30 (m, 1 H), 7.35 (d, J=8.34 Hz, 2 H), 7.47-7.54(m, 1 H), 7.68 (d, J=8.08 Hz, 1 H), 7.82 (d, J=8.59 Hz, 1 H), 7.89 (d,J=8.34 Hz, 2 H), 9.57 (s, 1 H). ESI-MS: m/z 377.8 (M+H)⁺.

Example 61N-(2-aminophenyl)-4-((3-chloro-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.87 (s, 2 H), 5.73-5.82 (m, 2 H),6.51-6.61 (m, 1 H), 6.74 (d, J=8.08 Hz, 1 H), 6.90-6.99 (m, 1 H),7.10-7.19 (m, 2 H), 7.29-7.37 (m, 3 H), 7.53 (s, 1 H), 7.57-7.68 (m, 2H), 7.93 (d, J=7.83 Hz, 2 H), 9.61 (s, 1 H). ESI-MS: m/z 377.8 (M+H)⁺.

Example 624-((3-amino-5-(trifluoromethyl)-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.86 (s, 2 H), 5.47 (s, 2 H), 6.53-6.60(m, 1 H), 6.73-6.80 (m, 3 H), 6.90-6.97 (m, 1 H), 7.13 (d, J=7.58 Hz, 1H), 7.20-7.25 (m, 1 H), 7.25-7.34 (m, 3 H), 7.90 (d, J=8.08 Hz, 2 H),8.17 (s, 1 H), 9.59 (s, 1 H). ESI-MS: m/z 425.5 (M+H)⁺.

Example 634-((3-amino-5-(trifluoromethyl)-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.85 (s, 2 H), 5.45 (s, 2 H), 5.85 (s, 2H), 6.56 (td, J=7.58, 1.26 Hz, 1 H), 6.74 (dd, J=8.08, 1.26 Hz, 1 H),6.89-6.97 (m, 1 H), 7.10 (s, 1 H), 7.28 (d, J=8.08 Hz, 2 H), 7.50-7.57(m, 1 H), 7.66 (d, J=8.84 Hz, 1 H), 7.87 (d, J=8.08 Hz, 2 H), 8.20 (s, 1H), 9.55 (s, 1 H). ESI-MS: m/z 425.5 (M+H)⁺.

Example 64N-(2-aminophenyl)-4-((3-oxo-2,3-dihydro-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 5.46(s, 2 H), 6.92 (s, 1 H), 7.01 (t, J=7.33 Hz, 2 H), 7.12 (s, 1 H), 7.25(s, 1 H), 7.33 (d, J=7,83 Hz, 3 H), 7.55 (d, J=8.34 Hz, 1 H), 7.64 (d,J=8.08 Hz, 1 H), 7.90 (d, J=7.58 Hz, 2 H), 9.92 (s, 1 H). ESI-MS: m/z359.3 (M+H)⁺.

Example 65N-(2-aminophenyl)-4-((3-oxo-1H-indazol-2(3H)-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 5.51(s, 2 H), 6.89 (s, 1 H), 7.02 (s, 2 H), 7.15 (s, 1 H), 7.27 (s, 1 H),7.37 (s, 2 H), 7.66 (s, 3 H), 8.02 (d, J=7.33 Hz, 2 H), 9.96 (s, 1 H),11.98 (s, 1 H). ESI-MS: m/z 359.3 (M+H)⁺.

Example 66N-(2-aminophenyl)-4-((6-methoxy-3-methyl-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.41-2.46 (m, 3 H), 3.78-3.84 (m, 3 H),4.88 (s, 2 H), 5.60 (s, 2 H), 6.54-6.62 (m, 1 H), 6.72-6.79 (m, 2 H),6.92-6.99 (m, 1 H), 7.11-7.18 (m, 2 H), 7.32 (d, J=8.34 Hz, 2 H), 7.58(d, J=8.59 Hz, 1 H), 7.90 (d, J=8.34 Hz, 2 H), 9.58 (s, 1 H). ESI-MS:m/z 387.2 (M+H)⁺.

Example 67N-(2-aminophenyl)-4-((6-methoxy-3-methyl-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.55 (s, 3 H), 3.79 (s, 3 H), 4.88 (s, 2H), 5.63 (s, 2 H), 6.55-6.62 (m, 1 H), 6.62-6.68 (m, 1 H), 6.77 (dd,J=7.83, 1.26 Hz, 1 H), 6.86 (d, J=2.02 Hz, 1 H), 6.93-7.00 (m, 1 H),7.14 (d, J=7.33 Hz, 1 H), 7.27 (d, J=8.34 Hz, 2 H), 7.55 (d, J=9.09 Hz,1 H), 7.93 (d, J=8.08 Hz, 2 H), 9.62 (s, 1 H). ESI-MS: m/z 387.2 (M+H)⁺.

Example 68N-(2-aminophenyl)-4-((6-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.47-2.49 (m, 3 H), 4.87 (s, 2 H), 5.61(s, 2 H), 6.55-6.61 (m, 1 H), 6.76 (dd, J=8.08, 1.52 Hz, 1 H), 6.93-7.02(m, 2 H), 7.14 (d, J=7.83 Hz, 1 H), 7.34 (d, J=8.34 Hz, 2 H), 7.54-7.61(m, 1 H), 7.77 (dd, J=8.84, 5.31 Hz, 1 H), 7.90 (d, J=8.34 Hz, 2 H),9.57 (s, 1 H). ESI-MS: m/z 375.3 (M+H)⁺.

Example 69N-(2-aminophenyl)-4-((6-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.59-2.63 (m, 3 H), 4.88 (s, 2 H), 5.69(s, 2 H), 6.53-6.62 (m, 1 H), 6.78 (dd, J=7.75, 1.52 Hz, 1 H), 6.87-6.99(m, 2 H), 7.15 (d, J=7.33 Hz, 1 H), 7.24-7.35 (m, 3 H), 7.77 (dd,J=9.09, 5.56 Hz, 1 H), 7.94 (d, J=8.08 Hz, 2 H), 9.62 (s, 1 H). ESI-MS:m/z 375.3 (M+H)⁺.

Example 70N-(2-aminophenyl)-4-((5-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.46-2.49 (m, 3 H), 4.87 (s, 2 H), 5.66(s, 2 H), 6.53-6.62 (m, 1 H), 6.77 (d, J=1.26 Hz, 1 H), 6.91-7.01 (m, 1H), 7.14 (d, J=7.07 Hz, 1 H), 7.25-7.35 (m, 3 H), 7.55 (d, J=2.27 Hz, 1H), 7.70 (dd, J=9.09, 4.29 Hz, 1 H), 7.89 (d, J=8.08 Hz, 2 H), 9.57 (s,1 H). ESI-MS: m/z 375.3 (M+H)⁺.

Example 71N-(2-aminophenyl)-4-((5-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.58 (s, 3 H), 4.88 (s, 2 H), 5.72 (s, 2H), 6.55-6.62 (m, 1 H), 6.77 (dd, J=8.08, 1.26 Hz, 1 H), 6.93-7.00 (m, 1H), 7.14 (td, J=9.35, 2.53 Hz, 2 H), 7.29 (d, J=8.34 Hz, 2 H), 7.46 (dd,J=9.60, 2.02 Hz, 1 H), 7.62 (dd, J=9.35, 4.55 Hz, 1 H), 7.94 (d, J=8.34Hz, 2 H), 9.62 (s, 1 H). ESI-MS: m/z 375.4 (M+H)⁺.

Example 72N-(2-aminophenyl)-4-((3-ethyl-1H-indazol-1-yl)methyl)benzamide

1H NMR (400 MHz, DMSO-d₆) δ ppm 1.29-1.36 (m, 3 H), 2.95 (q, J=7.58 Hz,2 H), 4.87 (s, 2 H), 5.67 (s, 2 H), 6.53-6.62 (m, 1 H), 6.72-6.81 (m, 1H), 6.91-7.00 (m, 1 H), 7.08-7.18 (m, 2 H), 7.27-7.39 (m, 3 H), 7.63 (d,J=8.34 Hz, 1 H), 7.77 (d, J=8.08 Hz, 1 H), 7.89 (d, J=8.08 Hz, 1 H),9.57 (s, 1 H). ESI-MS: m/z 371.4 (M+H)⁺.

Example 73N-(2-aminophenyl)-4-((3-ethyl-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.09-1.20 (m, 3 H), 3.09 (q, J=7.58 Hz,2 H), 4.89 (s, 2 H), 5.75 (s, 2 H), 6.55-6.62 (m, 1 H), 6.74-6.80 (m, 1H), 6.93-7.03 (m, 2 H), 7.14 (d, J=7.58 Hz, 1 H), 7.21-7.31 (m, 3 H),7.56 (d, J=8.84 Hz, 1 H), 7.72 (d, J=8.59 Hz, 1 H), 7.93 (d, J=8.34 Hz,2 H), 9.63 (s, 1 H). ESI-MS: m/z 371.4 (M+H)⁺.

Example 74N-(2-aminophenyl)-4-((6-hydroxy-3-methyl-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.42 (s, 3 H), 5.52 (s, 2 H), 6.59-6.69(m, 1 H), 6.74 (d, J=1.77 Hz, 1 H), 6.94 (s, 1 H), 7.04 (s, 1 H),7.08-7.20 (m, 2 H), 7.23-7.34 (m, 3 H), 7.50 (d, J=8.84 Hz, 1 H), 7.92(d, J=8.34 Hz, 2 H), 9.95 (s, 1 H). ESI-MS: m/z 373.3 (M+H)⁺.

Example 75N-(2-aminophenyl)-4-((6-hydroxy-3-methyl-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 2.54(s, 3 H), 3.97 (s, 1 H), 5.62 (s, 2 H), 6.56-6.65 (m, 1 H), 6.69 (d,J=1.52 Hz, 1 H), 7.01 (s, 1 H), 7.10 (d, J=7.83 Hz, 1 H), 7.14-7.23 (m,1 H), 7.30 (d, J=8.08 Hz, 3 H), 7.52 (d, J=8.84 Hz, 1 H), 7.96 (d,J=8.34 Hz, 2 H), 10.07 (s, 1 H). ESI-MS: m/z 373.3 (M+H)⁺.

Example 76N-(2-aminophenyl)-4-((3-phenyl-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.86 (s, 2 H), 5.78-5.87 (m, 2 H),6.53-6.61 (m, 1 H), 6.75 (dd, J=8.08, 1.26 Hz, 1 H), 6.91-6.99 (m, 1 H),7.13 (d, J=7.83 Hz, 1 H), 7.22-7.30 (m, 1 H), 7.38-7.49 (m, 3 H),7.50-7.57 (m, 2 H), 7.80 (d, J=8.34 Hz, 1 H), 7.91 (d, J=8.34 Hz, 2 H),8.00 (d, J=7.07 Hz, 2 H), 8.11 (d, J=8.08 Hz, 1 H), 9.57 (s, 1 H).ESI-MS: m/z 419.4 (M+H)⁺.

Example 77N-(2-aminophenyl)-4-((3-phenyl-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.87 (s, 2 H), 5.77 (s, 2 H), 6.54-6.61(m, 1 H), 6.76 (dd, J=8.08, 1.26 Hz, 1 H), 6.92-6.99 (m, 1 H), 7.09-7.17(m, 3 H), 7.30-7.37 (m, 1 H), 7.52-7.63 (m, 3 H), 7.69 (d, J=8.84 Hz, 1H), 7.89 (d, J=8.08 Hz, 2 H), 9.60 (s, 1 H). ESI-MS: m/z 419.4 (M+H)⁺.

Example 78N-(2-aminophenyl)-4-((5-methoxy-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 3.78(s, 3 H), 5.71 (s, 2 H), 6.53-6.64 (m, 1 H), 6.78 (s, 1 H), 6.91-7.00(m, 1 H), 7.01-7.08 (m, 1 H), 7.13 (s, 1 H), 7.20 (d, J=2.27 Hz, 1 H),7.30 (d, J=8.08 Hz, 2 H), 7.61 (d, J=9.09 Hz, 1 H), 7.89 (d, J=8.08 Hz,2 H), 8.01 (s, 1 H), 9.59 (s, 1 H). ESI-MS: m/z 373.3 (M+H)⁺.

Example 79N-(2-aminophenyl)-4-((5-methoxy-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.77 (s, 3 H), 5.69 (s, 2 H), 6.84-6.95(m, 2 H), 6.95-7.05 (m, 2 H), 7.07-7.15 (m, 1 H), 7.26 (d, J=7.58 Hz, 1H), 7.42 (d, J=8.34 Hz, 2 H), 7.51 (d, J=9.09 Hz, 1 H), 7.96 (d, J=8.34Hz, 2 H), 8.35 (s, 1 H), 9.91 (s, 1 H). ESI-MS: m/z 373.3 (M+H)⁺.

Example 80N-(2-aminophenyl)-4-((3,5-dimethyl-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.40 (s, 3 H), 2.44-2.48 (m, 3 H), 4.87(s, 2 H), 5.62 (s, 2 H), 6.54-6.61 (m, 1 H), 6.76 (dd, J=8.08, 1.26 Hz,1 H), 6.92-6.99 (m, 1 H), 7.13 (d, J=7.07 Hz, 1 H), 7.20 (dd, J=8.59,1.26 Hz, 1 H), 7.28 (d, J=8.08 Hz, 2 H), 7.49 (s, 1 H), 7.52 (d, J=8.59Hz, 1 H), 7.88 (d, J=8.08 Hz, 2 H), 9.57 (s, 1 H). ESI-MS: m/z 371.4(M+H)⁺.

Example 81N-(2-aminophenyl)-4-((3,5-dimethyl-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.36 (s, 3 H), 2.56 (s, 3 H), 4.88 (s, 2H), 5.69 (s, 2 H), 6.54-6.62 (m, 1 H), 6.77 (dd, J=8.08, 1.26 Hz, 1 H),6.93-7.00 (m, 1 H), 7.07 (dd, J=8.84, 1.52 Hz, 1 H), 7.14 (d, J=7.07 Hz,1 H), 7.26 (d, J=8.34 Hz, 2 H), 7.41 (s, 1 H), 7.45 (d, J=8.84 Hz, 1 H),7.93 (d, J=8.08 Hz, 2 H), 9.62 (s, 1 H). ESI-MS: m/z 371.4 (M+H)⁺.

Example 82N-(2-aminophenyl)-4-((7-methoxy-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.88 (s, 3 H), 4.89 (s, 2 H), 5.70 (s, 2H), 6.54-6.65 (m, 2 H), 6.76 (d, J=7.58 Hz, 1 H), 6.90-7.01 (m, 2 H),7.15 (s, 1 H), 7.24 (d, J=8.34 Hz, 1 H), 7.41 (d, J=7.58 Hz, 2 H), 7.95(d, J=8.08 Hz, 2 H), 8.47 (s, 1 H), 9.62 (s, 1 H). ESI-MS: m/z 373.1(M+H)⁺.

Example 83N-(2-aminophenyl)-4-((4-methoxy-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.89 (s, 3 H), 4.89 (s, 2 H), 5.69 (s, 2H), 6.36-6.46 (m, 1 H), 6.53-6.64 (m, 1 H), 6.76 (d, J=8.08 Hz, 1 H),6.91-7.02 (m, 1 H), 7.11-7.20 (m, 3 H), 7.42 (d, J=7.83 Hz, 2 H), 7.94(d, J=7.83 Hz, 2 H), 8.55 (s, 1 H), 9.62 (s, 1 H). ESI-MS: m/z 373.2(M+H)⁺.

Example 84N-(2-aminophenyl)-4-((7-methoxy-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.92 (s, 3 H), 4.87 (s, 2 H), 5.85 (s, 2H), 6.54-6.61 (m, 1 H), 6.76 (d, J=7.83 Hz, 1 H), 6.87 (d, J=7.58 Hz, 1H), 6.92-6.99 (m, 1 H), 7.03-7.10 (m, 1 H), 7.13 (d, J=7.83 Hz, 1 H),7.24 (d, J=7.83 Hz, 2 H), 7.32 (d, J=8.08 Hz, 1 H), 7.88 (d, J=7.58 Hz,2 H), 8.09 (s, 1 H), 9.56 (s, 1 H). ESI-MS: m/z 373.3 (M+H)⁺.

Example 85N-(2-aminophenyl)-4-((4-methoxy-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.93 (s, 3 H), 4.87 (s, 2 H), 5.72 (s, 2H), 6.54-6.63 (m, 2 H), 6.76 (d, J=7.83 Hz, 1 H), 6.90-7.00 (m, 1 H),7.13 (d, J=7.83 Hz, 1 H), 7.23-7.33 (m, 4 H), 7.89 (d, J=7.83 Hz, 2 H),8.10 (s, 1 H), 9.58 (s, 1 H). ESI-MS: m/z 373.3 (M+H)⁺.

Example 864-((6-acetamido-3-methyl-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.06 (s, 3 H), 2.53-2.57 (m, 2 H), 4.88(s, 2 H), 5.66 (s, 2 H), 6.53-6.63 (m, 1 H), 6.76 (dd, J=8.08, 1.26 Hz,1 H), 6.93-7.04 (m, 2 H), 7.14 (d, J=7.07 Hz, 1 H), 7.27 (d, J=8.08 Hz,2 H), 7.59 (d, J=9.09 Hz, 1 H), 7.93 (d, J=8.08 Hz, 2 H), 7.99 (s, 1 H),9.62 (s, 1 H), 9.91 (s, 1 H). ESI-MS: m/z 414.3 (M+H)⁺.

Example 874-((6-acetamido-3-methyl-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.06 (s, 3 H), 2.44-2.48 (m, 3 H), 4.88(s, 2 H), 5.56 (s, 2 H), 6.53-6.63 (m, 1 H), 6.73-6.81 (m, 1 H),6.91-7.01 (m, 1 H), 7.08-7.19 (m, 2 H), 7.24 (d, J=8.08 Hz, 2 H), 7.63(d, J=8.59 Hz, 1 H), 7.89 (d, J=8.08 Hz, 2 H), 8.01 (s, 1 H), 9.58 (s, 1H), 10.09 (s, 1 H). ESI-MS: m/z 414.3 (M+H)⁺.

Example 884-((3-amino-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.88 (s, 2 H), 5.46 (s, 2 H), 6.27 (s, 2H), 6.58 (t, J=7.45 Hz, 1 H), 6.65 (t, J=7.33 Hz, 1 H), 6.76 (d, J=8.08Hz, 1 H), 6.96 (t, J=7.58 Hz, 1 H), 7.05 (t, J=7.58 Hz, 1 H), 7.12-7.20(m, 2 H), 7.29 (d, J=7.83 Hz, 2 H), 7.63 (d, J=8.34, Hz, 1 H), 7.91 (d,J=7.83 Hz, 2 H), 9.6 (s, 1H). ESI-MS: m/z 358.2 (M+H)⁺.

Example 894-((6-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.93-2.13 (m, 3 H), 4.87 (s, 2 H), 5.66(s, 2 H), 6.53-6.61 (m, 1 H), 6.75 (dd, J=7.96, 1.39 Hz, 1 H), 6.91-6.98(m, 1 H), 7.13 (dd, J=8.72, 1.64 Hz, 2 H), 7.24 (d, J=8.34 Hz, 2 H),7.69 (d, J=8.59 Hz, 1 H), 7.90 (d, J=8.08 Hz, 2 H), 8.05 (s, 1 H), 8.08(s, 1 H), 9.59 (s, 1 H), 10.11 (s, 1 H). ESI-MS: m/z 400.2 (M+H)⁺.

Example 904-((6-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.06 (s, 3 H), 4.88 (s, 2 H), 5.67 (s, 2H), 6.51-6.65 (m, 1 H), 6.76 (dd, J=8.08, 1.26 Hz, 1 H), 6.89-7.00 (m, 1H), 7.06 (dd, J=8.84, 1.77 Hz, 1 H), 7.14 (d, J=7.33 Hz, 1 H), 7.40 (d,J=8.08 Hz, 2 H), 7.63 (d, J=8.34 Hz, 1 H), 7.94 (d, J=8.08 Hz, 2 H),8.04 (s, 1 H), 8.42 (s, 1 H), 9.62 (s, 1 H), 9.93 (s, 1 H). ESI-MS: m/z400.2 (M+H)⁺.

Example 91N-(2-aminophenyl)-4-((3-methyl-7-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.66 (s, 3 H), 4.89 (s, 2 H), 5.82 (s, 2H), 6.58 (t, J=7.45 Hz, 1 H), 6.76 (d, J=7.83 Hz, 1 H), 6.96 (t, J=7.58Hz, 1 H), 7.14 (ddd, J=7.26, 3.92, 3.73 Hz, 2 H), 7.28 (d, J=8.08 Hz, 2H), 7.66 (d, J=6.82 Hz, 1 H), 7.94 (d, J=8.08 Hz, 2 H), 8.05 (d, J=8.34Hz, 1 H), 9.62 (s, 1H). ESI-MS: m/z 425.2 (M+H)⁺.

Example 92N-(2-aminophenyl)-4-((3-methyl-6-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.67 (s, 3 H), 4.88 (s, 2 H), 5.80 (s, 2H), 6.58 (t, J=7.58 Hz, 1 H), 6.76 (d, J=7.83 Hz, 1 H), 6.96 (t, J=7.71Hz, 1 H), 7.14 (d, J=7.83 Hz, 1 H), 7.22 (d, J=8.84 Hz, 1 H), 7.30 (d,J=8.08 Hz, 2 H), 7.92-8.02 (m, 4 H), 9.63 (s, 1H). ESI-MS: m/z 425.2(M+H)⁺.

Example 93N-(2-aminophenyl)-4-((3-methyl-6-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.55 (s, 3 H), 4.87 (s, 2 H), 5.79 (s, 2H), 6.57 (t, J=7.33 Hz, 1 H), 6.75 (d, J=8.08 Hz, 1 H), 6.95 (t, J=7.58Hz, 1 H), 7.13 (d, J=7.58 Hz, 1 H), 7.33 (d, J=8.08 Hz, 2 H), 7.41 (d,J=8.59 Hz, 1 H), 7.90 (d, J=7.83 Hz, 2 H), 7.98 (d, J=8.34 Hz, 1 H),8.24 (s, 1 H), 9.58 (s, 1H). ESI-MS: m/z 425.2 (M+H)⁺.

Example 94N-(2-aminophenyl)-4-((3-methyl-5-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.57 (s, 3 H), 4.87 (s, 2 H), 5.73 (s, 2H), 6.57 (t, J=7.45 Hz, 1 H), 6.75 (d, J=7.83 Hz, 1 H), 6.95 (t, J=7.45Hz, 1 H), 7.13 (d, J=7.58 Hz, 1 H), 7.33 (d, J=7.83 Hz, 2 H), 7.67 (d,J=8.84 Hz, 1 H), 7.90 (d, J=8.34 Hz, 3 H), 8.22 (s, 1 H), 9.58 (s, 1H).ESI-MS: m/z 425.2 (M+H)⁺.

Example 95N-(2-aminophenyl)-4-((3-methyl-5-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.70 (s, 3 H), 4.88 (s, 2 H), 5.78 (s, 2H), 6.58 (t, J=7.45 Hz, 1 H), 6.76 (d, J=8.08 Hz, 1 H), 6.93-6.99 (m, 1H), 7.14 (d, J=7.33 Hz, 1 H), 7.31 (d, J=8.08 Hz, 2 H), 7.44 (d, J=8.84Hz, 1 H), 7.75 (d, J=9.09 Hz, 1 H), 7.94 (d, J=8.08 Hz, 2 H), 8.25 (s, 1H), 9.63 (s, 1H). ESI-MS: m/z 425.2 (M+H)⁺.

Example 964-((3-amino-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.87 (s, 2 H), 5.39 (s, 2 H), 5.52 (s, 2H), 6.57 (t, J=7.45 Hz, 1 H), 6.75 (d, J=7.83 Hz, 1 H), 6.94 (q, J=7.75Hz, 2 H), 7.13 (d, J=7.58 Hz, 1 H), 7.27 (t, J=8.21 Hz, 3 H), 7.44 (d,J=8.34 Hz, 1 H), 7.70 (d, J=7.83 Hz, 1 H), 7.86 (d, J=7.83 Hz, 2 H),9.55 (s, 1 H). ESI-MS: m/z 358.4 (M+H)⁺.

Example 97N-(2-aminophenyl)-4-((5-hydroxy-6-methoxy-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.81 (s, 2 H) 4.89 (s, 2 H) 5.58 (s, 2H), 6.59 (t, J=7.58 Hz, 1 H) 6.77 (dd, J=7.96, 1.39 Hz, 1 H) 6.85 (s, 1H) 6.91 (s, 1 H) 6.96 (dd, J=15.16, 1.52 Hz, 1 H) 7.15 (d, J=7.33 Hz, 1H) 7.36 (d, J=8.08 Hz, 2 H) 7.93 (d, J=8.08 Hz, 2 H) 8.11 (s, 1 H) 8.82(s, 1 H) 9.62 (s, 1 H). ESI-MS: m/z 389.4 (M+H)⁺.

Example 98N-(2-aminophenyl)-4-((5,6-dimethoxy-2H-indazol-2-yl)methyl)benzamide

5,6-dimethoxy-1H-indazole was prepared according to the proceduredescribed in Dennler et al., “Synthesis of indazoles usingpolyphosphoric acid-I” Tetrahedron, 22(9): 3131-3141 (1966), which ishereby incorporated by reference in its entirety. The title compound wasthen prepared using a procedure analogous to that described in Scheme 1.¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.78 (s, 3 H) 3.83 (s, 3 H) 4.88 (br.s., 2 H) 5.69 (s, 2 H) 6.58 (t, J=7.45 Hz, 1 H) 6.77 (d, J=1.01 Hz, 1 H)6.96 (dd, J=15.16, 1.26 Hz, 1 H) 7.17 (s, 1 H) 7.13 (d, J=7.58 Hz, 1 H)7.27 (s, 1 H) 7.30 (d, J=8.34 Hz, 2 H) 7.83-7.93 (m, 3 H) 9.59 (s, 1 H).ESI-MS: m/z 403.4 (M+H)⁺.

Example 99N-(2-aminophenyl)-4-((5,6-dimethoxy-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.78 (s, 3 H) 3.83 (s, 3 H) 4.88 (br.s., 2 H ) 5.69 (s, 2 H) 6.58 (s, 1 H) 6.77 (d, J=1.01 Hz, 1 H) 6.95 (d,J=7.33 Hz, 1 H) 7.17 (s, 1 H), 7.13 (d, J=7.58 Hz, 1 H) 7.27 (s, 1 H)7.30 (d, J=8.34 Hz, 2 H) 7.82-7.94 (m, 3 H) 9.59 (s, 1 H). ESI-MS: m/z403.4 (M+H)⁺.

Example 1004-((1H-benzo[d][1,2,3]triazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.88 (s, 2 H), 6.08 (s, 2 H), 6.57 (t,J=7.58 Hz, 1 H), 6.74-6.78 (m, 1 H), 6.93-6.98 (m, 1 H), 7.13 (d, J=7.58Hz, 1 H), 7.39-7.46 (m, 3 H), 7.55 (t, J=7.71 Hz, 1 H), 7.86 (d, J=8.34Hz, 1 H), 7.94 (d, J=8.08 Hz, 2 H), 8.07 (d, J=8.34 Hz, 1 H), 9.60 (s, 1H). ESI-MS: m/z 344.4 (M+H)⁺.

Example 1014-((2H-benzo[d][1,2,3]triazol-2-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.88 (s, 2 H), 6.07 (s, 2 H), 6.55-6.61(m, 1 H), 6.77 (dd, J=8.08, 1.26 Hz, 1 H), 6.93-6.99 (m, 1 H), 7.15 (d,J=7.58 Hz, 1 H), 7.43-7.48 (m, 2 H), 7.50 (d, J=8.34 Hz, 2 H), 7.91-7.99(m, 4 H), 9.63 (s, 1 H). ESI-MS: m/z 344.4 (M+H)⁺.

Example 1024-((5-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.05 (s, 3 H), 5.70 (s, 2 H), 6.95-7.03(m, 4 H), 7.06-7.13 (m, 1 H), 7.30-7.40 (m, 5 H), 7.64 (d, J=9.09 Hz, 1H), 7.75 (d, J=8.84 Hz, 2 H), 7.86 (d, J=8.08 Hz, 2 H), 8.11 (d, J=17.68Hz, 2 H), 9.96 (s, 1 H), 10.21 (s, 1 H). ESI-MS: m/z 477.3 (M+H)⁺.

Example 1031-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-(piperazin-1-yl)ethyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) of the bis-trifluoroacetic acid salt: δ ppm3.06 (s, 2 H), 3.22 (s, 4 H), 3.30 (s, 4 H), 3.44-3.52 (m, 2 H), 5.46(s, 2 H), 6.79 (t, J=3.33 Hz, 1 H), 6.93 (d, J=7.07 Hz, 1 H), 7.07 (td,J=7.64, 1.39 Hz, 1 H), 7.22 (d, J=8.59 Hz, 1 H), 7.38 (d, J=8.34 Hz, 2H), 7.90 (d, J=0.51 Hz, 1 H), 7.97 (d, J=8.08 Hz, 2 H), 8.29-8.32 (m, 1H), 8.32-8.35 (m, 1 H), 9.85 (s, 1 H). ESI-MS: m/z 448.4 (M+H)⁺.

Example 1044-((2H-indazol-2-yl)methyl)-N-(4-aminopyrimidin-5-yl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 5.74 (s, 2 H), 6.82 (s, 2 H), 7.00-7.08(m, 1 H), 7.23 (dd, J=8.72, 6.69 Hz, 1 H), 7.43 (d, J=8.34 Hz, 2 H),7.59 (d, J=8.84 Hz, 1 H), 7.72 (d, J=8.34 Hz, 1 H), 7.95 (d, J=8.08 Hz,2 H), 8.15 (s, 1 H), 8.26 (s, 1 H), 8.53 (s, 1 H), 9.64 (s, 1 H).ESI-MS: m/z 345.3 (M+H)⁺.

Example 1054-((5-acetamido-3-amino-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.03 (s, 3 H), 4.86 (s, 2 H), 5.35 (s, 2H), 5.43 (s, 2 H), 6.57 (t, J=7.45 Hz, 1 H), 6.75 (d, J=7.07 Hz, 1 H),6.92-6.98 (m, 1 H), 7.13 (d, J=7.33 Hz, 1 H), 7.24-7.31 (m, 3 H),7.35-7.41 (m, 1 H), 7.86 (d, J=7.83 Hz, 2 H), 7.96 (s, 1 H), 9.55 (s, 1H), 9.81 (s, 1 H). ESI-MS: m/z 415.3 (M+H)⁺.

Example 1064-((5-acetamido-3-methyl-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.05 (s, 3 H), 2.53 (s, 3 H), 4.88 (s, 2H), 5.68 (s, 2 H), 6.58 (t, J=7.45 Hz, 1 H), 6.76 (d, J=7.83 Hz, 1 H),6.93-6.98 (m, 1 H), 7.14 (d, J=7.83 Hz, 1 H), 7.20 (dd, J=9.22, 1.64 Hz,1 H), 7.27 (d, J=8.34 Hz, 2 H), 7.49 (d, J=9.09 Hz, 1 H), 7.93 (d,J=8.08 Hz, 2 H), 8.05 (s, 1 H), 9.62 (s, 1 H), 9.85 (s, 1 H). ESI-MS:m/z 414.3 (M+H)⁺.

Example 1074-((5-acetamido-3-methyl-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.04 (s, 3 H), 2.45 (s, 3 H), 4.87 (s, 2H), 5.61 (s, 2 H), 6.54-6.60 (m, 1 H), 6.75 (dd, J=7.96, 1.39 Hz, 1 H),6.92-6.98 (m, 1 H), 7.13 (d, J=7.33 Hz, 1 H), 7.30 (d, J=8.34 Hz, 2 H),7.38 (dd, J=9.09, 1.77 Hz, 1 H), 7.57 (d, J=8.84 Hz, 1 H), 7.88 (d,J=8.34 Hz, 2 H), 8.04 (d, J=1.26 Hz, 1 H), 9.57 (s, 1 H), 9.94 (s, 1 H).ESI-MS: m/z 414.3 (M+H)⁺.

Example 108 4-(1-(1H-indazol-1-yl)ethyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.97 (d, J=7.07 Hz, 3 H), 4.86 (s, 2 H),6.16 (q, J=6.99 Hz, 1 H), 6.57 (t, J=7.58 Hz, 1 H), 6.75 (d, J=6.82 Hz,1 H), 6.91-6.98 (m, 1 H), 7.13 (t, J=7.20 Hz, 2 H), 7.34 (t, J=7.58 Hz,1 H), 7.39 (d, J=8.34 Hz, 2 H), 7.66 (d, J=8.34 Hz, 1 H), 7.77 (d,J=8.08 Hz, 1 H), 7.87 (d, J=8.08 Hz, 2 H), 8.17 (s, 1 H), 9.55 (s, 1 H).ESI-MS: m/z 357.4 (M+H)⁺.

Example 109 4-(1-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.99 (d, J=7.07 Hz, 3 H), 4.88 (s, 2 H),6.04 (q, J=6.99 Hz, 1 H), 6.57 (t, J=7.58 Hz, 1 H), 6.76 (d, J=8.08 Hz,1 H), 6.91-6.99 (m, 1 H), 7.01-7.06 (m, 1 H), 7.14 (d, J=7.58 Hz, 1 H),7.20-7.26 (m, 1 H), 7.44 (d, J=8.34 Hz, 2 H), 7.61 (d, J=8.84 Hz, 1 H),7.71 (d, J=8.34 Hz, 1 H), 7.92 (d, J=8.34 Hz, 2 H), 8.56 (s, 1 H), 9.60(s, 1 H). ESI-MS: m/z 357.4 (M+H)⁺.

Example 1105-((5-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)thiophene-2-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.05 (s, 3 H), 4.86 (s, 2 H), 5.85 (s, 2H), 6.52-6.58 (m, 1 H), 6.74 (d, J=6.82 Hz, 1 H), 6.92-6.97 (m, 1 H),7.02-7.07 (m, 1 H), 7.16 (d, J=3.54 Hz, 1 H), 7.44 (dd, J=9.09, 1.77 Hz,1 H), 7.71 (d, J=9.09 Hz, 1 H), 7.78 (d, J=3.03 Hz, 1 H), 8.08 (s, 1 H),8.13 (d, J=1.26 Hz, 1 H), 9.62 (s, 1 H), 9.97 (s, 1 H). ESI-MS: m/z406.3 (M+H)⁺.

Example 1114-((2H-indazol-2-yl)methyl)-N-(2-amino-5-(thiophen-2-yl)phenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 5.75(s, 2 H), 6.98-7.09 (m, 3 H), 7.24 (ddd, J=8.46, 6.95, 1.26 Hz, 1 H),7.31-7.35 (m, 1 H), 7.39-7.47 (m, 4 H), 7.54 (d, J=2.02 Hz, 1 H), 7.60(dd, J=8.84, 1.01 Hz, 1 H), 7.73 (d, J=8.34 Hz, 1 H), 7.98 (d, J=8.34Hz, 2 H), 8.54 (d, J=1.01 Hz, 1 H), 9.96 (s, 1 H). ESI-MS: m/z 425.5(M+H)⁺.

Example 112N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4,6-difluoro-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 5.76(s, 2 H), 6.93 (s, 1 H), 7.07 (d, J=8.59 Hz, 2 H), 7.30 (d, J=3.28 Hz, 1H), 7.35-7.42 (m, 4 H), 7.50 (d, J=1.77 Hz, 1 H), 7.62 (d, J=9.35 Hz, 1H), 7.95 (d, J=8.08 Hz, 2 H), 8.30 (s, 1 H), 9.86 (s, 1 H). ESI-MS: m/z461.3 (M+H)⁺.

Example 113N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4,6-difluoro-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 5.74(s, 2 H), 6.85-6.97 (m, 2 H), 7.04-7.07 (m, 1 H), 7.24-7.29 (m, 2 H),7.34 (dd, J=8.34, 1.77 Hz, 1 H), 7.38 (d, J=5.05 Hz, 1 H), 7.45-7.50 (m,3 H), 7.98 (d, J=8.08 Hz, 2 H), 8.84 (s, 1 H), 9.81 (s, 1 H). ESI-MS:m/z 461.3 (M+H)⁺.

Example 114N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((6-methoxy-3-methyl-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 2.54(s, 3 H), 3.78 (s, 3 H), 5.64 (s, 2 H), 6.65 (d, J=9.09 Hz, 1 H), 6.86(s, 2 H), 7.05 (s, 1 H), 7.27 (s, 4 H), 7.37 (s, 1 H), 7.48 (s, 1 H),7.56 (s, 1 H), 7.96 (d, J=7.83 Hz, 2 H), 9.78 (s, 1 H). ESI-MS: m/z469.3 (M+H)⁺.

Example 115N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.02 (s, 3 H), 5.15 (s, 2 H), 5.34 (s, 2H), 6.80 (d, J=8.34 Hz, 1 H), 7.03-7.07 (m, 1 H), 7.24 (d, J=3.28 Hz, 1H), 7.27-7.33 (m, 4 H), 7.35 (d, J=5.05 Hz, 1 H), 7.46 (s, 1 H), 7.60(s, 1 H), 7.95 (d, J=7.83 Hz, 2 H), 9.71 (s, 1 H). ESI-MS: m/z389.3(M+H)⁺.

Example 116N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((6-methoxy-3-methyl-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 2.43(s, 3 H), 3.81 (s, 3 H), 5.61 (s, 2 H), 6.74 (dd, J=8.84, 2.02 Hz, 1 H),7.00 (d, J=8.34 Hz, 1 H), 7.08 (dd, J=5.05, 3.79 Hz, 1 H), 7.15 (d,J=2.02 Hz, 1 H), 7.35 (d, J=8.08 Hz, 3 H), 7.40-7.45 (m, 2 H),

Example 117N-(2-aminophenyl)-4-((4-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 5.88(s, 2 H), 6.95 (t, J=7.33 Hz, 1 H), 7.05 (d, J=7.33 Hz, 1 H), 7.11-7.18(m, 1 H), 7.27 (d, J=7.33 Hz, 1 H), 7.39 (d, J=8.34 Hz, 2 H), 7.59 (s, 1H), 7.60 (d, J=2.27 Hz, 1 H), 7.93 (d, J=8.08 Hz, 2 H), 8.10-8.17 (m, 1H), 8.27 (s, 1 H), 9.97 (s, 1 H). ESI-MS: m/z 411.3 (M+H)⁺.

Example 118N-(2-aminophenyl)-4-((4-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 5.83(s, 2 H), 7.11 (t, J=7.33 Hz, 1 H), 7.16-7.25 (m, 2 H), 7.34 (d,J=7.33Hz, 1 H), 7.38-7.44 (m, 1 H), 7.52 (d, J=8.08 Hz, 3 H), 7.95 (d, J=8.59Hz, 1 H), 7.99 (d, J=8.08 Hz, 2 H), 8.80 (s, 1 H), 10.16 (s, 1 H).ESI-MS: m/z 411.3 (M+H)⁺.

Example 119N-(2-aminophenyl)-4-((5-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 5.85(s, 2 H), 6.93 (t, J=7.20 Hz, 1 H), 7.03 (d, J=7.83 Hz, 1 H), 7.13 (t,J=7.07 Hz, 1 H), 7.25 (d, J=7.33 Hz, 1 H), 7.36 (d, J=8.08 Hz, 2 H),7.70 (dd, J=8.84, 1.52 Hz, 1 H), 7.91-7.99 (m, 3 H), 8.28 (s, 1 H), 8.34(s, 1 H), 9.95 (s, 1 H). ESI-MS: m/z 411.3 (M+H)⁺.

Example 120N-(2-aminophenyl)-4-((5-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 5.83(s, 2 H), 6.98 (t, J=7.45 Hz, 1 H), 7.07 (d, J=7.83 Hz, 1 H), 7.16 (t,J=7.20 Hz, 1 H), 7.29 (d, J=7.58 Hz, 1 H), 7.44-7.50 (m, 3 H), 7.81 (d,J=9.09 Hz, 1 H), 7.98 (d, J=8.08 Hz, 2 H), 8.28 (s, 1 H), 8.80 (s, 1 H),10.03 (s, 1 H). ESI-MS: m/z 411.3 (M+H)⁺.

Example 121N-(2-aminophenyl)-4-((6-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.90 (s, 2 H), 5.82 (s, 2 H), 6.59 (t,J=7.45 Hz, 1 H), 6.77 (d, J=7.07 Hz, 1 H), 6.94-6.99 (m, 1 H), 7.16 (d,J=7.58 Hz, 1 H), 7.45 (d, J=8.59 Hz, 3 H), 7.97 (d, J=8.34 Hz, 2 H),8.27 (s, 1 H), 8.74 (s, 1 H), 8.79 (s, 1 H), 9.65 (s, 1 H). ESI-MS: m/z411.3 (M+H)⁺.

Example 1221-(4-(2-aminophenylcarbamoyl)benzyl)-1H-pyrazole-4-carboxylic acid

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 5.47(s, 2 H), 6.93-6.99 (m, 1 H), 7.05 (d, J=7.33 Hz, 1 H), 7.15 (t, J=8.34Hz, 1 H), 7.28 (d, J=7.83 Hz, 1 H), 7.41 (d, J=8.34 Hz, 2 H), 7.85 (s, 1H), 7.97 (d, J=8.34 Hz, 2 H), 8.44 (s, 1 H), 10.01 (s, 1 H). ESI-MS: m/z337.3 (M+H)⁺.

Example 123N-(2-aminophenyl)-4-((3-methyl-1H-pyrazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 2.15(s, 3 H), 5.33 (s, 2 H), 6.07 (d, J=2.27 Hz, 1 H), 7.11-7.16 (m, 1 H),7.18-7.26 (m, 2 H), 7.34 (d, J=8.34 Hz, 2 H), 7.37 (dd, J=7.96, 0.88 Hz,1 H), 7.74 (d, J=2.02 Hz, 1 H), 7.98 (d, J=8.34 Hz, 2 H), 10.18 (s, 1H). ESI-MS: m/z 307.4 (M+H)⁺.

Example 124N-(2-aminophenyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 2.12(s, 3 H), 2.17 (s, 3 H), 5.30 (s, 2 H), 5.90 (s, 1 H), 7.10-7.15 (m, 1H), 7.16-7.20 (m, 1 H), 7.21-7.25 (m, 3 H), 7.35 (dd, J=7.83, 1.26 Hz, 1H), 7.96 (d, J=8.34 Hz, 2 H), 10.15 (s, 1 H). ESI-MS: m/z 321.4 (M+H)⁺.

Example 125 Ethyl1-(4-(2-aminophenylcarbamoyl)benzyl)-1H-pyrazole-4-carboxylate

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 1.27(t, J=7.07 Hz, 3 H), 4.22 (q, J=7.07 Hz, 2 H), 5.48 (s, 2 H), 6.99 (t,J=7.33 Hz, 1 H), 7.05-7.11 (m, 1 H), 7.14-7.20 (m, 1 H), 7.30 (d, J=7.83Hz, 1 H), 7.41 (d, J=8.34 Hz, 2 H), 7.90 (s, 1 H). 7.97 (d, J=8.08 Hz, 2H), 8.53 (s, 1 H), 10.04 (s, 1 H). ESI-MS: m/z 365.4 (M+H)⁺.

Example 1261-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridin-2-ylmethyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.49 (d, J=6.06 Hz, 2 H), 4.90 (s, 2H),5.45 (s, 2 H), 6.59 (td, J=7.45, 1.26 Hz, 1 H), 6.77 (dd, J=8.08, 1.26Hz, 1 H), 6.97 (td, J=7.58, 1.52 Hz, 1 H), 7.16 (d, J=7.07 Hz, 1 H),7.25 (ddd, J=7.58, 4.80, 1.01 Hz, 1 H), 7.30 (d, J=7.83 Hz, 1 H), 7.39(d, J=8.08 Hz, 2 H), 7.75 (td, J=7.64, 1.89 Hz, 1 H), 7.94-7.98 (m, 3H), 8.34 (s, 1 H), 8.50 (ddd, J=4.93, 1.89, 1.01 Hz, 1 H), 8.75 (t,J=5.94 Hz, 1 H), 9.65 (s, 1 H). ESI-MS: m/z 427.4 (M+H)⁺.

Example 1271-(4-(2-aminophenylcarbamoyl)benzyl)-N-phenyl-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.90 (s, 2 H), 5.49 (s, 2 H), 6.59 (td,J=7.52, 1.39 Hz, 1 H), 6.77 (dd, J=7.96, 1.39 Hz, 1 H), 6.97 (td,J=7.71, 1.52 Hz, 1 H), 7.04-7.09 (m, 1 H), 7.16 (d, J=7.33 Hz, 1 H),7.30-7.35 (m, 2 H), 7.40 (d, J=8.34 Hz, 2 H), 7.70 (dt, J=8.65, 1.61 Hz,2 H), 7.97 (d, J=8.08 Hz, 2 H), 8.09 (d, J=0.76 Hz, 1 H), 8.49 (s, 1 H),9.66 (s, 1 H), 9.86 (s, 1 H). ESI-MS: m/z 412.4 (M+H)⁺.

Example 1281-(4-(2-aminophenylcarbamoyl)benzyl)-N-benzyl-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.41 (d, J=6.06 Hz, 2 H), 4.90 (s, 2 H),5.44 (s, 2 H), 6.59 (td, J=7.52, 1.39 Hz, 1 H), 6.77 (dd, J=7.96, 1.39Hz, 1 H), 6.97 (td, J=7.58, 1.52 Hz, 1 H), 7.15 (d, J=7.07 Hz, 1 H),7.21-7.25 (m, 1 H), 7.27-7.34 (m, 4 H), 7.38 (d, J=8.34 Hz, 2 H), 7.95(s, 2 H), 7.97 (s, 1 H), 8.32 (s, 1 H), 8.65 (t, J=6.06 Hz, 1 H), 9.65(s, 1 H). ESI-MS: m/z 426.4 (M+H)⁺.

Example 129N-(2-aminophenyl)-4-((4,5,6,7-tetrahydro-2H-indazol-2-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm1.63-1.74 (m, 4 H), 2.45-2.49 (m, 4 H), 5.27 (s, 2 H), 6.90-6.98 (m, 1H), 7.04 (d, J=8.59 Hz, 1 H), 7.14 (t, J=7.83 Hz, 1 H), 7.28 (d, J=7.58Hz, 1 H), 7.36 (d, J=8.34 Hz, 2 H), 7.50 (s, 1 H), 7.94 (d, J=8.34 Hz, 2H), 9.96 (s, 1 H). ESI-MS: m/z 347.4 (M+H)⁺.

Example 130N-(2-aminophenyl)-4-((4,5,6,7-tetrahydro-1H-indazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm1.59-1.66 (m, 2 H), 1.68-1.76 (m, 2 H), 2.44 (t, J=5.94 Hz, 2 H),2.47-2.50 (m, 2 H), 5.31 (s, 2 H), 7.04 (t, J=7.33 Hz, 1 H), 7.10-7.13(m, 1 H), 7.16-7.21 (m, 1 H), 7.23-7.27 (m, 3 H), 7.31 (dd, J=7.96, 1.14Hz, 1 H), 7.95 (d, J=8.34 Hz, 2 H), 10.07 (s, 1 H). ESI-MS: m/z 347.4(M+H)⁺.

Example 131 4-((1H-pyrazol-3-ylamino)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 4.42(s, 2 H), 5.74 (d, J=2.53 Hz, 1 H), 6.85 (t, J=7.45 Hz, 1 H), 6.96-7.00(m, 1 H), 7.10 (td, J=7.64, 1.39 Hz, 1 H), 7.23-7.27 (m, 1 H), 7.48 (d,J=8.34 Hz, 2 H), 7.80 (d, J=2.78 Hz, 1 H), 7.97 (d, J=8.34 Hz, 2 H),9.89 (s, 1 H). ESI-MS: m/z 308.4 (M+H)⁺.

Example 1324-((5-amino-1H-pyrazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.89 (s, 2 H), 5.19 (s, 2 H), 5.29 (s, 2H), 5.31 (d, J=2.02 Hz, 1 H), 6.59 (td, J=7.52, 1.39 Hz, 1 H), 6.77 (dd,J=8.08, 1.52 Hz, 1 H), 6.96 (td, J=7.58, 1.52 Hz, 1 H), 7.10 (d, J=2.02Hz, 1 H), 7.15 (d, J=6.82 Hz, 1 H), 7.22 (d, J=8.34 Hz, 2 H), 7.90 (d,J=8.08 Hz, 2 H), 9.60 (s, 1 H). ESI-MS: m/z 308.4 (M+H)⁺.

Example 1334-((3-amino-1H-pyrazol-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.59 (s, 2 H), 4.89 (s, 2 H), 5.11 (s, 2H), 5.44 (d, J=2.27 Hz, 1 H), 6.59 (td, J=7.58, 1.26 Hz, 1 H), 6.77 (dd,J=8.08, 1.52 Hz, 1 H), 6.96 (td, J=7.58, 1.52 Hz, 1 H), 7.16 (d, J=7.83Hz, 1 H), 7.28 (d, J=8.08 Hz, 2 H), 7.48 (d, J=2.02 Hz, 1 H), 7.91 (d,J=8.08 Hz, 2 H), 9.61 (s, 1 H). ESI-MS: m/z 308.4 (M+H)⁺.

Example 1341-(4-(2-aminophenylcarbamoyl)benzyl)-N-methyl-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.70 (d, J=4.55 Hz, 3 H), 4.89 (s, 2 H),5.43 (s, 2 H), 6.59 (td, J=7.52, 1.14 Hz, 1 H), 6.77 (dd, J=8.08, 1.26Hz, 1 H), 6.94-6.99 (m, 1 H), 7.15 (d, J=7.33 Hz, 1 H), 7.35 (d, J=8.34Hz, 2 H), 7.86 (s, 1 H), 7.95 (d, J=8.08 Hz, 2 H), 8.05 (q, J=4.55 Hz, 1H), 8.25 (s, 1 H), 9.64 (s, 1 H). ESI-MS: m/z 350.3 (M+H)⁺.

Example 1351-(4-(2-aminophenylcarbamoyl)benzyl)-N-ethyl-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.07 (t, J=7.20 Hz, 3 H), 3.16-3.24 (m,2 H), 4.89 (s, 2 H), 5.43 (s, 2 H), 6.59 (td, J=7.58, 1.26 Hz, 1 H),6.77 (dd, J=7.96, 1.39 Hz, 1 H), 6.96 (td, J=7.71, 1.52 Hz, 1 H), 7.15(d, J=8.34 Hz, 1 H), 7.35 (d, J=8.34 Hz, 2 H), 7.87 (d, J=0.76 Hz, 1 H),7.95 (d, J=8.34 Hz, 2 H), 8.07 (t, J=5.43 Hz, 1 H), 8.25 (s, 1 H), 9.64(s, 1 H). ESI-MS: m/z 364.4 (M+H)⁺.

Example 1361-(4-(2-aminophenylcarbamoyl)benzyl)-N,N-dimethyl-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.97 (m, 3 H), 3.14 (m, 3 H), 4.90 (s, 2H), 5.44 (s, 2 H), 6.59 (t, J=7.71 Hz, 1 H), 6.77 (dd, J=7.83, 1.01 Hz,1 H), 6.94-6.99 (m, 1 H), 7.15 (d, J=7.83 Hz, 1 H), 7.37 (d, J=8.34 Hz,2 H), 7.77 (s, 1 H), 7.95 (d, J=8.34 Hz, 2 H), 8.31 (s, 1 H), 9.63 (s, 1H). ESI-MS: m/z 364.3 (M+H)⁺.

Example 1371-(4-(2-aminophenylcarbamoyl)benzyl)-N-isopropyl-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.11 (d, J=6.82 Hz, 6 H), 4.02 (dq,J=13.80, 6.77 Hz, 1 H), 4.89 (s, 2 H), 5.43 (s, 2 H), 6.56-6.61 (m, 1H), 6.77 (dd, J=8.08, 1.26 Hz, 1 H), 6.97 (td, J=7.58, 1.26 Hz, 1 H),7.15 (d, J=7.58 Hz, 1 H), 7.36 (d, J=8.08 Hz, 2 H), 7.83 (d, J=7.83 Hz,1 H), 7.89 (s, 1 H), 7.96 (d, J=8.08 Hz, 2 H), 8.26 (s, 1 H), 9.64 (s, 1H), ESI-MS: m/z 378.4 (M+H)⁺.

Example 1381-(4-(2-aminophenylcarbamoyl)benzyl)-N-cyclopropyl-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.48 (m, 2 H), 0.65 (m, 2 H), 2.70-2.77(m, J=7.31, 7.31, 3.92, 3.74, 3.74 Hz, 1 H), 4.90 (s, 2 H), 5.42 (s, 2H), 6.56-6.62 (m, 1 H), 6.77 (dd, J=8.08, 1.26 Hz, 1 H), 6.94-6.99 (m, 1H), 7.15 (d, J=7.33 Hz, 1 H), 7.35 (d, J=8.08 Hz, 2 H), 7.87 (s, 1 H),7.95 (d, J=8.08 Hz, 2 H), 8.08 (d, J=3.79 Hz, 1 H), 8.25 (s, 1 H), 9.64(s, 1 H). ESI-MS: m/z 376.3 (M+H)⁺.

Example 1391-(4-(2-aminophenylcarbamoyl)benzyl)-N-(cyclopropylmethyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.17-0.21 (m, 2 H), 0.39-0.44 (m, 2 H),0.91-1.01 (m, 1 H), 3.07 (t, J=6.32 Hz, 2 H), 4.90 (s, 2 H), 5.44 (s, 2H), 6.59 (t, J=7.45 Hz, 1 H), 6.77 (dd, J=8.08, 1.01 Hz, 1 H), 6.94-6.99(m, 1 H), 7.15 (d, J=7.58 Hz, 1 H), 7.37 (d, J=8.08 Hz, 2 H), 7.90 (s, 1H), 7.96 (d, J=8.08 Hz, 2 H), 8.17 (t, J=5.68 Hz, 1 H), 8.28 (s, 1 H),9.65 (s, 1 H). ESI-MS: m/z 390.4 (M+H)⁺.

Example 1401-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-(dimethylamino)ethyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) of the bis-trifluoroacetic acid salt: δ ppm2.52-2.55 (m, 2 H), 2.83 (d, J=4.80 Hz, 6 H), 3.17-3.23 (m, 2 H), 5.46(s, 2 H), 6.61-6.68 (m, 1 H), 6.82 (d, J=7.33 Hz, 1 H), 6.97-7.03 (m, 1H), 7.16 (d, J=8.59 Hz, 1 H), 7.38 (d, J=7.83 Hz, 2 H), 7.90 (s, 1 H),7.96 (d, J=8.34 Hz, 2 H), 8.30 (s, 1 H), 8.34 (t, J=6.06 Hz, 1 H), 9.70(s, 1 H). ESI-MS: m/z 407.4 (M+H)⁺.

Example 1411-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-(dimethylamino)ethyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 2.23 (s, 6 H), 2.47-2.49 (m, 2 H),3.27-3.33 (m, 2 H), 4.89 (s, 2 H), 5.44 (s, 2 H), 6.59 (td, J=7.52, 1.39Hz, 1 H), 6.77 (dd, J=8.08, 1.52 Hz, 1 H), 6.94-6.99 (m, 1 H), 7.15 (d,J=8.34 Hz, 1 H), 7.36 (d, J=8.34 Hz, 2 H), 7.88 (s, 1 H), 7.95 (d,J=8.34 Hz, 2 H), 8.04 (t, J=5.81 Hz, 1 H), 8.27 (s, 1 H), 9.64 (s, 1 H).ESI-MS: m/z 407.4 (M+H)⁺.

Example 1421-(4-(2-aminophenylcarbamoyl)benzyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.90 (s, 2 H), 5.43 (s, 2 H), 6.56-6.62(m, 1 H), 6.77 (dd, J=8.08, 1.26 Hz, 1 H), 6.94-6.99 (m, 1 H), 7.03 (s,1 H), 7.15 (d, J=7.33 Hz, 1 H), 7.36 (d, J=8.08 Hz, 2 H), 7.58 (s, 1 H),7.88 (s, 1 H), 7.96 (d, J=8.34 Hz, 2 H), 8.26 (s, 1 H), 9.64 (s, 1 H).ESI-MS: m/z 336.3 (M+H)⁺.

Example 1431-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-hydroxyethyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.24 (q, J=5.98 Hz, 2 H), 3.45 (q,J=6.15 Hz, 2 H), 4.69-4.72 (m, 1 H), 4.89 (s, 2 H), 5.43 (s, 2 H), 6.59(td, J=7.52, 1.39 Hz, 1 H), 6.77 (dd, J=8.08, 1.52 Hz, 1 H), 6.97 (td,J=7.71, 1.52 Hz, 1 H), 7.15 (d, J=7.58 Hz, 1 H), 7.36 (d, J=8.34 Hz, 2H), 7.90 (d, J=0.51 Hz, 1 H), 7.95 (d, J=8.34 Hz, 2 H), 8.09 (t, J=5.68Hz, 1 H), 8.28 (d, J=0.76 Hz, 1 H), 9.64 (s, 1 H). ESI-MS: m/z 380.3(M+H)⁺.

Example 1441-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-(dimethylamino)propyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.59 (qd, J=7.07, 6.82 Hz, 2 H), 2.12(s, 6 H), 2.23 (t, J=7.20 Hz, 2 H), 3.16-3.22 (m, 2 H), 4.89 (s, 2 H),5.43 (s, 2 H), 6.59 (td, J=7.52, 1.39 Hz, 1 H), 6.77 (dd, J=8.08, 1.52Hz, 1 H), 6.97 (td, J=7.58, 1.52 Hz, 1 H), 7.15 (d, J=7.33 Hz, 1 H),7.36 (d, J=8.08 Hz, 2 H), 7.87 (d, J=0.76 Hz, 1 H), 7.95 (d, J=8.34 Hz,2 H), 8.10 (t, J=5.68 Hz, 1 H), 8.25 (d, J=0.51 Hz, 1 H), 9.64 (s, 1 H).ESI-MS: m/z 421.4 (M+H)⁺.

Example 1451-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridin-3-ylmethyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.42 (d, J=5.81 Hz, 2 H), 4.89 (s, 2 H),5.44 (s, 2 H), 6.59 (td, J=7.52, 1.39 Hz, 1 H), 6.77 (dd, J=7.96, 1.39Hz, 1 H), 6.97 (td, J=7.58, 1.52 Hz, 1 H), 7.15 (d, J=7.33 Hz, 1 H),7.33-7.36 (m, 1 H), 7.36-7.39 (m, 2 H), 7.83, 2.02 Hz, 1 H), 7.93 (d,J=0.51 Hz, 1 H), 7.95 (d, J=8.08 Hz, 2 H), 8.32 (d, J=0.51 Hz, 1 H),8.45 (dd, J=4.80, 1.77 Hz, 1 H), 8.52 (d, J=1.52 Hz, 1 H), 8.70 (t,J=5.94 Hz, 1 H), 9.64 (s, 1 H). ESI-MS: m/z 427.3 (M+H)⁺.

Example 1461-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridin-4-ylmethyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 4.43 (d, J=6.06 Hz, 2 H), 4.90 (s, 2 H),5.46 (s, 2 H), 6.59 (td, J=7.52, 1.39 Hz, 1 H), 6.77 (dd, J=7.96, 1.39Hz, 1 H), 6.94-6.99 (m, 1 H), 7.15 (d, J=7.33 Hz, 1 H), 7.26-7.29 (m, 2H), 7.39 (d, J=8.34 Hz, 2 H), 7.93-7.98 (m, 3 H), 8.34 (s, 1 H),8.48-8.50 (m, 2 H), 8.75 (t, J=6.06 Hz, 1 H), 9.65 (s, 1 H). ESI-MS: m/z427.3 (M+H)⁺.

Example 1471-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-morpholinoethyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) of the bis-trifluoroacetic acid salt: δ ppm3.07-3.19 (m, 2 H), 3.26 (t, J=6.19 Hz, 2 H), 3.49-3.59 (m, 4 H),3.59-3.71 (m, 2 H), 4.00 (d, J=13.64 Hz, 2 H), 5.46 (s, 2 H), 6.79 (t,J=7.20 Hz, 1 H), 6.93 (d, J=7.07 Hz, 1 H), 7.05-7.10 (m, 1 H), 7.22 (d,J=7.07 Hz, 1 H), 7.39 (d, J=8.34 Hz, 2 H), 7.91 (d, J=0.51 Hz, 1 H),7.97 (d, J=8.34 Hz, 2 H), 8.32 (d, J=0.51 Hz, 1 H), 8.42 (t, J=5.68 Hz,1 H), 9.85 (s, 1 H). ESI-MS: m/z 449.4 (M+H)⁺.

Example 148N-(2-aminophenyl)-4-((5-methyl-1H-pyrazol-1-yl)methyl)benzamide

¹H NMR (400 MHz, DMSO-d₆) of the trifluoroacetic acid salt: δ ppm 2.22(s, 3 H), 5.40 (s, 2 H), 6.11 (dd, J=2.15, 1.14 Hz, 1 H), 7.05 (t,J=7.58 Hz, 1 H), 7.11-7.15 (m, 1 H), 7.19 (d, J=7.33 Hz, 1 H), 7.22 (d,J=8.08 Hz, 2 H), 7.32 (d, J=7.83 Hz, 1 H), 7.39 (d, J=1.77 Hz, 1 H),7.96 (d, J=8.08 Hz, 2 H), 10.09 (s, 1 H). ESI-MS: m/z 307.3 (M+H)⁺.

Example 1491-(4-(2-aminophenylcarbamoyl)benzyl)-N-propyl-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.86 (t, J=7.33 Hz, 3 H), 1.43-1.52 (m,J=7.23, 7.23, 7.23, 7.23, 7.23 Hz, 2 H), 3.11-3.17 (m, 2 H), 4.90 (s, 2H), 5.43 (s, 2 H), 6.59 (td, J=7.45, 1.26 Hz, 1 H), 6.77 (dd, J=7.96,1.39 Hz, 1 H), 6.97 (td, J=7.71, 1.52 Hz, 1 H), 7.15 (d, J=7.83 Hz, 1H), 7.36 (d, J=8.34 Hz, 2 H), 7.89 (d, J=0.51 Hz, 1 H), 7.96 (d, J=8.08Hz, 2 H), 8.06 (t, J=5.68 Hz, 1 H), 8.26 (s, 1 H), 9.64 (s, 1 H).ESI-MS: m/z 378.3 (M+H)⁺.

Example 1501-(4-(2-aminophenylcarbamoyl)benzyl)-N-isobutyl-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.86 (d, J=6.57 Hz, 6 H), 1.76 (tt,J=13.52, 6.82 Hz, 1 H), 2.98-3.02 (m, 2 H), 4.90 (s, 2 H), 5.43 (s, 2H), 6.59 (td, J=7.58, 1.26 Hz, 1 H), 6.77 (dd, J=8.08, 1.26 Hz, 1 H),6.97 (td, J=7.58, 1.52 Hz, 1 H), 7.15 (d, J=7.58 Hz, 1 H), 7.37 (d,J=8.34 Hz, 2 H), 7.91 (d, J=0.51 Hz, 1 H), 7.96 (d, J=8.08 Hz, 2 H),8.06 (t, J=5.94 Hz, 1 H), 8.27 (s, 1 H), 9.64 (s, 1 H). ESI-MS: m/z392.4 (M+H)⁺.

Example 1511-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-methoxyethyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 3.25 (s, 3 H), 3.33-3.36 (m, 2 H),3.38-3.42 (m, 2 H), 4.89 (s, 2 H), 5.43 (s, 2 H), 6.59 (td, J=7.52, 1.39Hz, 1 H), 6.77 (dd, J=8.08, 1.26 Hz, 1 H), 6.97 (td, J=7.64, 1.39 Hz, 1H), 7.15 (d, J=7.07 Hz, 1 H), 7.36 (d, J=8.34 Hz, 2 H), 7.90 (d, J=0.51Hz, 1 H), 7.95 (d, J=8.08 Hz, 2 H), 8.16 (t, J=5.43 Hz, 1 H), 8.28 (d,J=0.51 Hz, 1 H), 9.64 (s, 1 H). ESI-MS: m/z 394.3 (M+H)⁺.

Example 1521-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-methoxypropyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.66-1.73 (m, 2 H), 3.18-3.22 (m, 1 H),3.22 (s, 4 H), 3.33 (t, J=3.16 Hz, 2 H), 4.89 (s, 2 H), 5.43 (s, 2 H),6.59 (td, J=7.58, 1.26 Hz, 1 H), 6.77 (dd, J=7.96, 1.39 Hz, 1 H), 6.97(td, J=7.58, 1.52 Hz, 1 H), 7.15 (d, J=7.33 Hz, 1 H), 7.36 (d, J=8.34Hz, 2 H), 7.88 (d, J=0.76 Hz, 1 H), 7.95 (d, J=8.08 Hz, 2 H), 8.08 (t,J=5.68 Hz, 1 H), 8.26 (d, J=0.76 Hz, 1 H), 9.64 (s, 1 H). ESI-MS: m/z408.4 (M+H)⁺.

Example 1531-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-hydroxypropyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.62 (qd, J=6.74, 6.57 Hz, 2 H), 3.23(q, J=6.65 Hz, 2 H), 3.40-3.46 (m, 2 H), 4.46 (t, J=5.31 Hz, 1 H), 4.90(s, 2 H), 6.59 (td, J=7.52, 1.39 Hz, 1 H), 6.77 (dd, J=8.08, 1.26 Hz, 1H), 6.97 (td, J=7.58, 1.52 Hz, 1 H), 7.15 (d, J=7.07 Hz, 1 H), 7.36 (d,J=8.08 Hz, 2 H), 7.89 (d, J=0.51 Hz, 1 H), 7.96 (d, J=8.08 Hz, 2 H),8.07 (t, J=5.68 Hz, 1 H), 8.26 (d, J=0.51 Hz, 1 H), 9.64 (s, 1 H).ESI-MS: m/z 394.3 (M+H)⁺.

Example 1541-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-morpholinopropyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) of the bis-trifluoroacetic acid salt: δ ppm1.83-1.91 (m, 2 H), 3.01-3.10 (m, 2 H), 3.10-3.17 (m, 2 H), 3.26 (q,J=6.32 Hz, 2 H), 3.43 (d, J=11.87 Hz, 2 H), 3.64 (t, J=11.87 Hz, 2 H),3.97 (d, J=11.87 Hz, 2 H), 5.46 (s, 2 H), 6.93 (t, J=7.07 Hz, 1 H), 7.04(dd, J=8.08, 1.26 Hz, 1 H), 7.11-7.17 (m, 1 H), 7.28 (d, J=8.84 Hz, 1H), 7.39 (d, J=8.34 Hz, 2 H), 7.91 (s, 1 H), 7.98 (d, J=8.08 Hz, 2 H),8.29-8.35 (m, 2 H), 10.00 (s, 1 H). ESI-MS: m/z 463.4 (M+H)⁺.

Example 1551-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-(piperidin-1-yl)ethyl)-1H-pyrazole-4-carboxamide

1H NMR (400 MHz, DMSO-d₆) of the bis-trifluoroacetic acid salt: δ ppm1.32-1.43 (m, 1 H), 1.60-1.71 (m, 3 H), 1.81 (d, J=14.40 Hz, 2 H),2.87-2.97 (m, 2 H), 3.18 (d, J=5.31 Hz, 2 H), 3.49-3.59 (m, 4 H), 5.47(s, 2 H), 6.94 (t, J=6.95 Hz, 1 H), 7.05-7.08 (m, 1 H), 7.15 (td,J=7.64, 1.39 Hz, 1 H), 7.30 (d, J=6.82 Hz, 1 H), 7.40 (d, J=8.34 Hz, 2H), 7.92 (d, J=0.76 Hz, 1 H), 7.99 (d, J=8.08 Hz, 2 H), 10.02 (s, 1 H).ESI-MS: m/z 447.4 (M+H)⁺.

Example 1561-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-(4-methylpiperazin-1-yl)propyl)-1H-pyrazole-4-carboxamide

¹H NMR (400 MHz, DMSO-d₆) of the bis-trifluoroacetic acid salt: δ ppm1.80-1.88 (m, 2 H), 2.84 (s, 3 H), 3.06-3.13 (m, 2 H), 3.26-3.60 (m, 10H), 5.45 (s, 2 H), 6.91 (t, J=6.95 Hz, 1 H), 7.03 (dd, J=8.08, 1.26 Hz,1 H), 7.13 (td, J=7.58, 1.52 Hz, 1 H), 7.27 (d, J=8.84 Hz, 1 H), 7.39(d, J=8.34 Hz, 2 H), 7.91 (d, J=0.76 Hz, 1 H), 7.98 (d, J=8.34 Hz, 2 H),8.30 (d, J=0.76 Hz, 1 H), 9.98 (s, 1 H). ESI-MS: m/z 476.4 (M+H)⁺.

Example 1574-((1H-Pyrrolo[2,3-b]pyridin-1-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-D6) of the trifluoroacetic acid salt: δ ppm 6.03(s, 2 H) 6.67 (s, 1 H) 6.83 (s, 1 H) 6.91-7.02 (m, 2 H) 7.12 (d, J=7.33Hz, 1 H) 7.31-7.40 (m, 2 H), 7.45 (d, J=8.34 Hz, 1 H) 7.58-7.70 (m, 1 H)7.87-7.99 (m, 2 H) 8.65-8.80 (m, 2 H), 9.76 (s, 1 H). ESI-MS: m/z 343.4(M+H)⁺.

Example 158 4-((1H-Indol-3-yl)methyl)-N-(2-aminophenyl)benzamide

¹H NMR (400 MHz, DMSO-D6) δ ppm 4.10 (s, 2 H) 4.84 (s, 2 H) 6.53-6.60(m, 1 H) 6.74 (d, J=7.83 Hz, 1 H) 6.88-6.97 (m, 2 H) 7.00-7.07 (m, 2 H)7.11 (s, 1 H), 7.19 (d, J=2.27 Hz, 1 H) 7.32 (d, J=8.08 Hz, 1 H)7.36-7.42 (m, 2 H) 7.85 (d, J=8.08 Hz, 2 H), 9.54 (s, 1 H) 10.87 (s, 1H). ESI-MS: m/z 342.4 (M+H)⁺.

In addition to the examples described above, the following non-limitinggroup of compounds can be prepared utilizing the above reaction schemes,and variations thereof, with the appropriate selection of substituents:

4-((1H-indazol-1-yl)methyl)-N-(2-amino-5- fluorophenyl)benzamide

4-((2H-indazol-2-yl)methyl)-N-(2-amino-5- fluorophenyl)benzamide

4-((1H-indazol-1-yl)methyl)-N-(2-amino-5-fluorophenyl)-3-methylbenzamide

4-((2H-indazol-2-yl)methyl)-N-(2-amino-5-fluorophenyl)-3-methylbenzamide

N-(2-aminophenyl)-3-methyl-4-((3-methyl-1H-indazol-1-yl)methyl)benzamide

N-(2-aminophenyl)-3-methyl-4-((3-methyl-2H-indazol-2-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3-cyano-1H-indazol- 1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3-cyano-2H- indazol-2-yl)methyl)benzamide

1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H- indazole-3-carboxylic acid

2-(4-((2-aminophenyl)carbamoyl)benzyl)- 2H-indazole-3-carboxylic acid

N-(2-aminophenyl)-4-((5-cyano-1H-indazol- 1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((5-cyano-2H- indazol-2-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3-(pyridin-2-yl)-1H- indazol-1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3-(pyridin-2-yl)-2H- indazol-2-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3-(dimethylamino)-1H-indazol-1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3-(dimethylamino)-2H-indazol-2-yl)methyl)benzamide

4-((1H-indazol-1-yl)methyl)-N-(2-amino-5- (furan-2-yl)phenyl)benzamide

4-((2H-indazol-2-yl)methyl)-N-(2-amino-5- (furan-2-yl)phenyl)benzamide

N-(2-aminophenyl)-4-((3-methoxy-1H- indazol-1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3-methoxy-2H- indazol-2-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3- (methoxymethylamino)-1H-indazol-1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3 - (methoxymethylamino)-2H-indazol-2-yl)methyl)benzamide

4-((1H-pyrazol-1-yl)methyl)-N-(2-amino-5- fluorophenyl)benzamide

N-(2-amino-5-fluorophenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide

4-((1H-pyrazol-1-yl)methyl)-N-(2- aminophenyl)-3-methylbenzamide

N-(2-amino-5-fluorophenyl)-3-methyl-4- ((4-methyl-1H-pyrazol-1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((4-(furan-2-yl)-1H- pyrazol-1-yl)methyl)benzamide

1-(4-((2-aminophenyl)carbamoyl)benzyl)- 1H-pyrazole-4-carboxylic acid

N-(2-aminophenyl)-4-((3-ethyl-1H-pyrazol-1- yl)methyl)benzamide

N-(2-aminophenyl)-4-((5-ethyl-1H-pyrazol- 1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((4-phenyl-1H-pyrazol- 1-yl)methyl)benzamide

N-(2-aminophenyl)-3-methyl-4-((5-methyl- 4-phenyl-1H-pyrazol-1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3-cyano-1H-pyrazol- 1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((5-(pyridin-2-yl)-1H- pyrazol-1-yl)methyl)benzamide

4-((1H-pyrazol-1-yl)methyl)-N-(2-amino-5- (furan-2-yl)phenyl)benzamide

N-(2-amino-5-(furan-2-yl)phenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide

(S)-4-(1-(1H-pyrazol-1-yl)ethyl)-N-(2- aminophenyl)benzamide

(R)-4-(1-(1H-pyrazol-1-yl)ethyl)-N-(2- aminophenyl)benzamide

N-(2-aminophenyl)-4-((3-(pyridin-2-yl)-1H- pyrazol-1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((5-methoxy-1H- pyrazol-1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3- (methoxymethylamino)-1H-pyrazol-1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((5- (methoxymethylamino)-1H-pyrazol-1-yl)methyl)benzamide

N-(2-aminophenyl)-4-((3-methoxy-1H- pyrazol-1-yl)methyl)benzamideBiological Testing

The activity of compounds as HDAC inhibitors may be assayed in vitro, invivo or in a cell line. Further, compounds according to the presentinvention may be screened for activity against one or more HDACs.Provided below are assays for activity against HDAC 1, HDAC2, HDAC6 andHDAC8.

Purified HDAC1, HDAC2, HDAC6, and HDAC8 may be obtained as follows.

For HDAC 1, DNA encoding residues 1-482 of the full-length sequence ofthe human enzyme may be amplified by PCR and cloned into the BamHI/XbaIsites of pFastbac (Invitrogen), which incorporates a Flag tag at boththe N— and C-terminus. SEQ ID NO: 1 corresponds to residues 1-482 withthe N-and C-terminal Flag tag and SEQ ID NO: 2 is the DNA sequence thatwas used to encode SEQ ID NO: 1.

For HDAC2, DNA encoding residues 1-488 of the full-length sequence ofthe human enzyme may be amplified by PCR and cloned into the BamHI/SmaIsites of pFastbac (Invitrogen), which incorporates a 6-histidine tag atthe C-terminus. SEQ ID NO: 3 corresponds to residues 1-488 with theC-terminal 6-histidine tag and SEQ ID NO: 4 is the DNA sequence that wasused to encode SEQ ID NO: 3.

For HDAC6, DNA encoding residues 73-845 of the human enzyme may beamplified by PCR and cloned into the SmaI site of pFastbac (Invitrogen),which incorporates a 6× Histidine tag at the C-terminus. SEQ ID NO: 5corresponds to residues 73-845 with the C-terminal 6-histidine tag andSEQ ID NO: 6 is the DNA sequence that was used to encode SEQ ID NO: 5.

For HDAC8, DNA encoding residues 1-377 corresponding to the entiresequence of the human enzyme may be amplified by PCR and cloned into theBamHI/SmaI sites of pFastbac (Invitrogen), which incorporates a6-histidine tag at the N-terminus. SEQ ID NO: 7 corresponds to residues1-377 with the N-terminal 6-histidine tag and SEQ ID NO: 8 is the DNAsequence that was used to encode SEQ ID NO: 7.

Recombinant baculovirus incorporating the HDAC constructs may begenerated by transposition using the Bac-to-Bac system (Invitrogen).High-titer viral stocks may be generated by infection of Spodopterafrugiperda Sf9 cells; the expression of recombinant protein may becarried out by infection of Spodoptera frugiperda Sf9 or Trichoplusia niHi5 cells (Invitrogen) in 10 L Wave Bioreactors (Wave Biotech).

Recombinant protein may be isolated from cellular extracts by passageover ProBond resin (Invitrogen), or Anti-Flag M2 Affinity Gel (Sigma)for HDAC 1. Partially purified HDAC 1 may then be further purified byhigh pressure liquid chromatography over a Mono Q column. Partiallypurified extracts of HDACs other than HDAC1 and HDAC6 may then befurther purified by high pressure liquid chromatography over a BioSepS3000 gel filtration resin. The purity of HDAC proteins may bedetermined on denaturing SDS-PAGE gel. Purified HDACs may then beconcentrated to a final concentration of 0.6 mg/ml for HDAC1, 10 mg/mlfor HDAC2, 0.3 mg/ml for HDAC6, and 3 mg/ml for HDAC8. The proteins maybe either stored at −78° C. in a buffer containing 25 mM TRIS-HCl pH7.6, 150mM NaCl, 0.1 mM EDTA and 0.25 mM TCEP or at −20° C. in thepresence of glycerol (final concentration of glycerol at 50%).Alternatively, HDAC6 protein can be stored at −78° C. in a buffercontaining 25 mM TRIS-HCl pH 7.2, 250 mM NaCl, and 5% glycerol.

It should be noted that a variety of other expression systems and hostsare also suitable for the expression of HDAC, as would be readilyappreciated by one of skill in the art.

The inhibitory properties of compounds relative to HDAC1, HDAC2, HDAC6and HDAC8 may be determined using a white or black 384-well-plate formatunder the following reaction conditions: 25 mM Tris pH 8.0, 100 mM NaCl,50 mM KCl, 0.1 mM EDTA, 0.01% Brij35, 0.1 mM TCEP. 50 μMtBoc-Lys(Ac)-AMC, 2% DMSO. Reaction product may be determinedquantitatively by fluorescence intensity using a Fluorescence platereader (Molecular Devices Gemini) with an excitation wavelength at 370nm and emission at 480 nm (for white plates) or 465 nm (for blackplates).

The assay reaction may be initiated as follows: 5 μl of 150 μMtBoc-Lys(Ac)AMC was added to each well of the plate, followed by theaddition of 5 μl of inhibitor (2 fold serial dilutions for 11 datapoints for each inhibitor) containing 6% DMSO. 5 μl of either HDAC1,HDAC2, HDAC6 or HDAC8 solution may be added to initiate the reaction(final enzyme concentrations were 2.5 nM for HDAC1, 1 nM for HDAC2, 2.5nM for HDAC6 and 10 nM for HDAC8). The reaction mixture may then beincubated at room temperature for 60 minutes, and quenched and developedby addition of 5 μl of 10 mM phenanthroline and 4 mg/ml trypsin (finalconcentration of phenanthroline is 2.5 mM, and trypsin is 1 mg/ml).Fluorescence intensities of the resulting reaction mixtures may bemeasured after a 30 minute incubation at room temperature.

IC50 values may be calculated by non-linear curve fitting of thecompound concentrations and fluorescence intensities to the standardIC50 equation. As a reference point for this assay, suberanilohydroxamicacid (SAHA) showed an IC₅₀ of 63 nM for HDAC1, 69 nM for HDAC2, 108 nMfor HDAC6 and 242 nM for HDAC8. IC₅₀ values for selected compounds ofthe present invention are given in Table 4. TABLE 4 IC₅₀ of SELECTEDEXEMPLIFIED COMPOUNDS AGAINST HDAC2 EXAMPLE IC₅₀ 1. ≦50 NM 2. 50-100 NM3. ≦50 NM 4. ≦50 NM 5. ≦50 NM 6. ≦50 NM 7. ≦50 NM 8. ≦50 NM 9. 50-100 NM10. ≦50 NM 11. ≦50 NM 12. ≦50 NM 13. ≦50 NM 14. ≦50 NM 15. ≦50 NM 16.≦50 NM 17. ≦50 NM 18. ≦50 NM 19. 100-500 NM 20. ≦50 NM 21. ≦50 NM 22.≦50 NM 23. ≦50 NM 24. 100-500 NM 25. 100-500 NM 26. ≦50 NM 27. ≦50 NM28. 50-100 NM 29. 50-100 NM 30. 50-100 NM 31. ≧500 NM 32. ≦50 NM 33.≧500 NM 34. 100-500 NM 35. 50-100 NM 36. 50-100 NM 37. 50-100 NM 38. ≦50NM 39. ≧500 NM 40. 100-500 NM 41. 50-100 NM 42. ≦50 NM 43. ≦50 NM 44.50-100 NM 45. 50-100 NM 46. 50-100 NM 47. 50-100 NM 48. 50-100 NM 49.≦50 NM 50. 50-100 NM 51. 50-100 NM 52. 50-100 NM 53. 50-100 NM 54.100-500 NM 55. 50-100 NM 56. 50-100 NM 57. 50-100 NM 58. 50-100 NM 59.≦50 NM 60. 50-100 NM 61. ≦50 NM 62. ≦50 NM 63. 50-100 NM 64. 50-100 NM65. 100-500 NM 66. ≦50 NM 67. ≦50 NM 68. 50-100 NM 69. 50-100 NM 70.100-500 NM 71. 50-100 NM 72. 50-100 NM 73. 100-500 NM 74. ≦50 NM 75.100-500 NM 76. 50-100 NM 77. 50-100 NM 78. ≦50 NM 79. ≦50 NM 80. 50-100NM 81. 50-100 NM 82. 50-100 NM 83. ≦50 NM 84. 100-500 NM 85. ≦50 NM 86.≦50 NM 87. 50-100 NM 88. 50-100 NM 89. ≦50 NM 90. ≦50 NM 91. 50-100 NM92. 50-100 NM 93. 50-100 NM 94. 50-100 NM 95. ≦50 NM 96. 50-100 NM 97.50-100 NM 98. ≦50 NM 99. ≦50 NM 100. 50-100 NM 101. 50-100 NM 102. ≧500NM 103. ≦50 NM 104. ≧500 NM 105. 50-100 NM 106. ≦50 NM 107. 50-100 NM108. 50-100 NM 109. 50-100 NM 110. 50-100 NM 111. ≦50 NM 112. 100-500 NM113. 100-500 NM 114. 50-100 NM 115. ≦50 NM 116. 50-100 NM 117. 50-100 NM118. 50-100 NM 119. 50-100 NM 120. 50-100 NM 121. ≦50 NM 122. ≧500 NM123. 100-500 NM 124. 100-500 NM 125. 50-100 NM 126. ≦50 NM 127. ≦50 NM128. ≦50 NM 129. 50-100 NM 130. 100-500 NM 131. ≧500 NM 132. ≧500 NM133. 100-500 NM 134. 50-100 NM 135. 50-100 NM 136. 100-500 NM 137. ≦50NM 138. 50-100 NM 139. 50-100 NM 140. 50-100 NM 141. 50-100 NM 142.50-100 NM 143. 50-100 NM 144. ≦50 NM 145. ≦50 NM 146. ≦50 NM 147. 50-100NM 148. 100-500 NM 149. ≦50 NM 150. ≦50 NM 151. 50-100 NM 152. ≦50 NM153. ≦50 NM 154. ≦50 NM 155. ≦50 NM 156. 50-100 NM 157. 100-500 NM 158.50-100 NM

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the compounds, compositions,kits, and methods of the present invention without departing from thespirit or scope of the invention. Thus, it is intended that the presentinvention cover the modifications and variations of this inventionprovided they come within the scope of the appended claims and theirequivalents.

1. A compound comprising:

wherein: n is selected from the group consisting of 0, 1, 2, 3 and 4; A₁is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; J₁ isselected from the group consisting of —CR₇R₇′— and —NR₁₉—; J₂ isselected from the group consisting of —CR₂₀R₂₀′ and —NR₁₀—; R₁ and R₂are each independently selected from the group consisting of hydrogen,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring; R₃ is selected from the groupconsisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈-₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; each R₄ is selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; R₅, R₅′, R₆, R₆′, R₇, R₇′, R₂₀ and R₂₀′are each independently selected from the group consisting of hydrogen,halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈-₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇, R₇′,R₂₀ and R₂₀′ may be taken together to form a substituted orunsubstituted ring, provided that R₅, R₆, R₇ and R₂₀, are eachindependently absent when the C to which they are bound is bound to L,and R₅′, R₆′, R₇′ and R₂₀′, are each independently absent when the C towhich they are bound form part of a double bond; and R₈, R₁₀ and R₁₉ areeach individually selected from the group consisting of hydrogen,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′, R₂₀, R₂₀′, R₁₀ and R₁₉ may be taken together to form a substitutedor unsubstituted ring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′, R₇, R₇′,R₂₀, R₂₀′, and R₁₉, may be taken together to form a substituted orunsubstituted ring, or R₁₉ and any one of R₅, R₅′, R₆, R₆′, R₂₀, andR₂₀′, may be taken together to form a substituted or unsubstituted ring,provided that R₈, R₁₀ and R₁₉ are each independently absent when the Nto which they are bound is bound to L, and R₈, R₁₀ and R₁₉ are eachindependently absent when the N to which they are bound form part of adouble bond.
 2. The compound according to claim 1 comprising

wherein: R₅, R₅′, R₆, R₆′, R₇ and R₇′ are each independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, oxo, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇ and R₇′may be taken together to form a substituted or unsubstituted ring,provided that R₅, R₆ and R₇ are each independently absent when the C towhich they are bound is bound to L, and R₅′, R₆′ and R₇′ are eachindependently absent when the C to which they are bound form part of adouble bond; and R₈ and R₁₀ are each individually selected from thegroup consisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈-₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′ and R₁₀ may be taken together to form a substituted or unsubstitutedring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′, R₇ and R₇′ may be takentogether to form a substituted or unsubstituted ring, provided that R₈and R₁₀ are each independently absent when the N to which they are boundis bound to L, and R₈ and R₁₀ are each independently absent when the Nto which they are bound form part of a double bond.
 3. The compoundaccording to claim 2, wherein the compound is selected from the groupconsisting of:

wherein: R₅, R₅′, R₆, R₆′, R₇ and R₇′ are each independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, oxo, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl,hetero(C₃₋₁₂)bicycloallkyl, aryl, heteroaryl, (C₉₋₁₂)bicycloaryl andhetero(C₄₋₁₂)bicycloaryl, each substituted or unsubstituted, or any twoof R₅, R₅′, R₆, R₆′, R₇ and R₇′ may be taken together to form asubstituted or unsubstituted ring, provided that R₅′, R₆′ and R₇′ areeach independently absent when the C to which they are bound form partof a double bond; and R₈ and R₁₀ are each individually selected from thegroup consisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′ and R₁₀ may be taken together to form a substituted or unsubstitutedring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′, R₇ and R₇′ may be takentogether to form a substituted or unsubstituted ring, provided that R₈and R₁₀ are each independently absent when the N to which they are boundform part of a double bond.
 4. The compound according to claim 3,wherein the compound is selected from the group consisting of:

wherein: R₁₁ is selected from the group consisting of hydrogen, halo,nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted.
 5. The compound according to claim 3,wherein the compound is selected from the group consisting of:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4;each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and any one of R₃,R₅, R₅′, R₇, R₇′, R₈ and R₁₀ may be taken together to form a substitutedor unsubstituted ring.
 6. The compound according to claim 3, wherein thecompound is selected from the group consisting of:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4;each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and any one of R₃,R₅, R₅′, R₇, R₇′, R₈ and R₁₀ may be taken together to form a substitutedor unsubstituted ring; and R₁₁ is selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring.
 7. The compound according toclaim 3, wherein the compound is selected from the group consisting of:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4;each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and any one of R₅,R₅′, R₇, R₇′, R₈ and R₁₀ may be taken together to form a substituted orunsubstituted ring; and R₁₁ is selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring.
 8. The compound according toclaim 3, wherein the compound is selected from the group consisting of:

wherein: p is selected from the group consisting of 0, 1, 2, 3 and 4; R₇is selected from the group consisting of hydrogen, halo, nitro, cyano,oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; R₁₁ is selected from the group consistingof hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C3-12)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₇ may be taken together toform a substituted or unsubstituted ring; and each R₁₂ is independentlyselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.
 9. The compound accordingto claim 3, wherein the compound is selected from the group consistingof:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4; pis selected from the group consisting of 0, 1, 2, 3 and 4; R₇ isselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; each R₉ is independently selected from thegroup consisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉, or one R₉ and R₃ may betaken together to form a substituted or unsubstituted ring; and each R₁₂is independently selected from the group consisting of hydrogen, halo,nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ may be taken together toform a substituted or unsubstituted ring.
 10. The compound according toclaim 3, wherein the compound is selected from the group consisting of:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4; pis selected from the group consisting of 0, 1, 2, 3 and 4; R₇ isselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; each R₉ is independently selected from thegroup consisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and R₃ may betaken together to form a substituted or unsubstituted ring; R₁₁ isselected from the group consisting of hydrogen, halo, nitro, cyano,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring; and each R₁₂ is independentlyselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.
 11. The compound accordingto claim 3, wherein the compound is selected from the group consistingof:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4; pis selected from the group consisting of 0, 1, 2, 3 and 4; R₇ isselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; each R₉ is independently selected from thegroup consisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ may be taken together toform a substituted or unsubstituted ring; R₁₁ is selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₇ or R₉ may be taken togetherto form a substituted or unsubstituted ring; and each R₁₂ isindependently selected from the group consisting of hydrogen, halo,nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.
 12. The compound accordingto claim 1, wherein the compound is selected from the group consistingof:

wherein: R₅, R₅′, R₆ and R₆′ are each independently selected from thegroup consisting of hydrogen, halo, nitro, cyano, oxo, thio, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,amido, carboxamido, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆ and R₆ 40 may betaken together to form a substituted or unsubstituted ring, providedthat R₅′ and R₆′ are each independently absent when the C to which theyare bound form part of a double bond; and R₈, R₁₀ and R₁₉, are eachindividually selected from the group consisting of hydrogen, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₁₀and R₁₉ may be taken together to form a substituted or unsubstitutedring, or R₁₀ and any one of R₅, R₅′, R₆, R₆′ and R₁₉ may be takentogether to form a substituted or unsubstituted ring, or R₁₉ and any oneof R₅, R₅′, R₆ and R₆′ may be taken together to form a substituted orunsubstituted ring, provided that R₈, R₁₀ and R₁₉ are each independentlyabsent when the N to which they are bound form part of a double bond.13. The compound according to claim 12, wherein the compound is selectedfrom the group consisting of:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4;each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and any one of R₃,R₅, R₅′, R₈, R₁₀ and R₁₉ may be taken together to form a substituted orunsubstituted ring; and R₁₁ is selected from the group consisting ofhydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring.
 14. The compound according toclaim 12, wherein the compound is selected from the group consisting of:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4; pis selected from the group consisting of 0, 1, 2, 3 and 4; each R₉ isindependently selected from the group consisting of hydrogen, halo,nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and R₃ may betaken together to form a substituted or unsubstituted ring; R₁₁ isselected from the group consisting of hydrogen, halo, nitro, cyano,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring; and each R₁₂ is independentlyselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₁₁ may be taken together toform a substituted or unsubstituted.
 15. The compound according to claim12, wherein the compound is selected from the group consisting of:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4; pis selected from the group consisting of 0, 1, 2, 3 and 4; each R₉ isindependently selected from the group consisting of hydrogen, halo,nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ may be taken together toform a substituted or unsubstituted ring; R₁₁ is selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxyl, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring; and each R₁₂ is independentlyselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxyl, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamide, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₁₁ may be taken together toform a substituted or unsubstituted ring.
 16. The compound according toclaim 1, wherein the compound is selected from the group consisting of:

wherein: R₅, R₅′, R₆, R₆′, R₇, R₇′, R₂₀ and R₂₀′ are each independentlyselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₅′, R₆, R₆′, R₇, R₇′,R₂₀ and R₂₀′ may be taken together to form a substituted orunsubstituted ring, provided that R₅′, R₆′, R₇′ and R₂₀′ are eachindependently absent when the C to which they are bound form part of adouble bond; and R₈ is selected from the group consisting of hydrogen,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₈ and any one of R₅, R₅′, R₆, R₆′, R₇,R₇′, R₂₀ and R₂₀′ may be taken together to form a substituted orunsubstituted ring, provided that R₈ is absent when the N to which it isbound forms part of a double bond.
 17. The compound according to claim16, wherein the compound is selected from the group consisting of:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4;each R₉ is independently selected from the group consisting of hydrogen,halo, nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and any one of R₃,R₅, R₅′, R₆, R₆′, R₇, R₇′, R₂₀, R₂₀′ and R₈ may be taken together toform a substituted or unsubstituted ring; and R₁₁ is selected from thegroup consisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring.
 18. The compound according toclaim 16, wherein the compound is selected from the group consisting of:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4; pis selected from the group consisting of 0, 1, 2, 3 and 4; each R₉ isindependently selected from the group consisting of hydrogen, halo,nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ or one R₉ and R₃ may betaken together to form a substituted or unsubstituted ring; R₁₁ isselected from the group consisting of hydrogen, halo, nitro, cyano,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring; and each R₁₂ is independentlyselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₁₁ may be taken together toform a substituted or unsubstituted ring.
 19. The compound according toclaim 16, wherein the compound is selected from the group consisting of:

wherein: m is selected from the group consisting of 0, 1, 2, 3 and 4; pis selected from the group consisting of 0, 1, 2, 3 and 4; each R₉ isindependently selected from the group consisting of hydrogen, halo,nitro, cyano, thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl,amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl,(C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two R₉ may be taken together toform a substituted or unsubstituted ring; R₁₁ is selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₁ and R₉ may be taken together toform a substituted or unsubstituted ring; and each R₁₂ is independentlyselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₁₁ may be taken together toform a substituted or unsubstituted ring.
 20. The compound according toclaim 1, wherein R₁ and R₂ are each independently selected from thegroup consisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl and imino(C₁₋₃)alkyl, each substituted or unsubstituted.21. The compound according to claim 1, wherein R₁ is hydrogen or asubstituent convertible in vivo to hydrogen.
 22. The compound accordingto claim 1, wherein R₂ is hydrogen or a substituent convertible in vivoto hydrogen.
 23. The compound according to claim 1, wherein R₃ ishydrogen or a substituent convertible in vivo to hydrogen.
 24. Thecompound according to claim 1, wherein R₄ is selected from the groupconsisting of hydrogen, halo, aryl and heteroaryl, each substituted orunsubstituted.
 25. The compound according to claim 1, wherein R₄ isselected from the group consisting of phenyl, oxazolyl, thiazolyl,morpholinyl and thiomorpholinyl, each substituted or unsubstituted. 26.The compound according to claim 1, wherein R₅, R₆, R₇ and R₂₀ are eachindependently selected from the group consisting of carbonyl, oxo,amino, (C₁₋₁₀)alkylamino, amido, carboxamido, cyano, alkoxy,(C₁₋₁₀)alkyl, aryl, and heteroaryl, each substituted or unsubstituted.27. The compound according to claim 1, wherein R₅ and R₆ are takentogether to form a substituted or unsubstituted ring.
 28. The compoundaccording to claim 1, wherein R₅ and R₆ are taken together to form aring selected from the group consisting of aryl and heteroaryl, eachsubstituted or unsubstituted.
 29. The compound according to claim 1,wherein the ring formed by R₅ and R₆ is substituted with a substituentselected from the group consisting of halo, alkoxy, amino(C₁₋₁₀)alkoxy,amino(C₁₋₁₀)alkylamino, amino(C₁₋₁₀)alkylsulfanyl, amido, carboxamido,halo(C₁₋₁₀)alkyl, aryl and heteroaryl, each substituted orunsubstituted.
 30. The compound according to claim 1, wherein the ringformed by R₅ and R₆ is substituted with a substituent selected from thegroup consisting of thiopheneyl, pyridinyl, furanyl and pyrimidinyl,each substituted or unsubstituted.
 31. The compound according to claim1, wherein the ring formed by R₅ and R₆ is substituted with—O—CH₂CH₂—NR₁₃R₁₄, wherein R₁₃ and R₁₄ are each independently selectedfrom the group consisting of hydrogen, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl, hetero(C₈₋₁₂)bicycloaryl (C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₃ and R₁₄ may be taken together toform a substituted or unsubstituted ring.
 32. The compound according toclaim 31, wherein R₁₃ and R₁₄ are each independently selected from thegroup consisting of hydrogen, (C₁₋₁₀)alkyl, (C₃₋₁₂)cycloalkyl, andheteroaryl, each substituted or unsubstituted.
 33. The compoundaccording to claim 31, wherein R₁₃ and R₁₄ are taken together to form aring selected from the group consisting of morpholinyl, pyrrolidinyl,piperazinyl and thiomorpholinyl, each substituted or unsubstituted. 34.The compound according to claim 1, wherein the ring formed by R₅ and R₆is substituted with —NH—CH₂CH₂—NR₁₃R₁₄, wherein R₁₃ and R₁₄ are eachindependently selected from the group consisting of hydrogen, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero (C₈₋₁₂)bicycloaryl (C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloarylsubstituted or unsubstituted, or R₁₃ and R₁₄ may be taken together toform a substituted or unsubstituted ring.
 35. The compound according toclaim 34, wherein R₁₃ and R₁₄ are each independently selected from thegroup consisting of hydrogen, (C₁₋₁₀)alkyl, (C₃₋₁₂)cycloalkyl, andheteroaryl, each substituted or unsubstituted.
 36. The compoundaccording to claim 34, wherein R₁₃ and R₁₄ are taken together to form aring selected from the group consisting of morpholinyl, pyrrolidinyl,piperazinyl and thiomorpholinyl, each substituted or unsubstituted. 37.The compound according to claim 1, wherein the ring formed by R₅ and R₆is substituted with —S—CH₂CH₂—NR₁₃R₁₄, wherein R₁₃ and R₁₄ are eachindependently selected from the group consisting of hydrogen, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero (C₈₋₁₂)bicycloaryl (C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloarylsubstituted or unsubstituted, or R₁₃ and R₁₄ may be taken together toform a substituted or unsubstituted ring.
 38. The compound according toclaim 37, wherein R₁₃ and R₁₄ are each independently selected from thegroup consisting of hydrogen, (C₁₋₁₀)alkyl, (C₃₋₁₂)cycloalkyl, andheteroaryl, each substituted or unsubstituted.
 39. The compoundaccording to claim 37, wherein R₁₃ and R₁₄ are taken together to form aring selected from the group consisting of morpholinyl, pyrrolidinyl,piperazinyl and thiomorpholinyl, each substituted or unsubstituted. 40.The compound according to claim 1, wherein R₈, R₁₀ and R₁₉ are eachindependently selected from the group consisting of hydrogen andsubstituted or unsubstituted (C₁₋₁₀)alkyl.
 41. The compound according toclaim 1, wherein L is a linker providing a 1-5 atom separation betweenthe two ring atoms to which L is attached.
 42. The compound according toclaim 1, wherein L is a linker providing a 1-3 atom separation betweenthe two ring atoms to which L is attached.
 43. The compound according toclaim 1, wherein L is a substituted or unsubstituted alkylene.
 44. Thecompound according to claim 1, wherein L is —CH₂—.
 45. The compoundaccording to claim 1, wherein L is selected from the group consisting of—NR₁₅—; —NR₁₅—CH₂—; —O—CH₂—; —CH₂—; —CH₂—NR₁₅—; —CH₂—O— and —CH₂—S—,wherein R₁₅ is selected from the group consisting of hydrogen, hydroxy,alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted.
 46. The compound according to claim 1,wherein A₁ is selected from the group consisting of aryl and heteroaryl,each substituted or unsubstituted.
 47. The compound according to claim1, wherein A₁ is a substituted or unsubstituted phenylene.
 48. Thecompound according to claim 1, wherein A₁ is a substituted orunsubstituted 1,4-phenylene.
 49. The compound according to claim 1,wherein A₁ is selected from the group consisting of a thiophenediyl,furandiyl, pyrrolediyl, thiazolediyl, oxazolediyl, imidazolediyl andpyridinediyl, each substituted or unsubstituted.
 50. The compoundaccording to claim 1, wherein A₁ comprises:

wherein: each X is independently selected from the group consisting ofCR₁₆ and N; and each R₁₆ is independently selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₆ is absent when the C to which it isbound is further bound to L or the carbonyl adjacent to A₁.
 51. Thecompound according to claim 1 1, wherein m is 0, R₁₁ is hydrogen, andR₁₂ is selected from the group consisting of hydroxyl, alkoxy, halo,amido, carboxamido, and (C₁₋₁₀)alkylamido, each substituted orunsubstituted.
 52. The compound according to claim 51, wherein n is 0, pis 2, and R₁₂ is selected from the group consisting of hydroxyl, alkoxy,and halo.
 53. The compound according to claim 52, wherein R₇ ishydrogen, and R₁₂ is alkoxy.
 54. A compound selected from the groupconsisting of: 4-((1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;4-((5-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((5-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((5-nitro-1H-indazol-1-yl)methyl)benzamide;4-((5-benzamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((5-amino-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((5-nitro-2H-indazol-2-yl)methyl)benzamide;4-((5-amino-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;4-((5-benzamido-2H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;2-Methoxyethyl2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate; Methyl2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate;2-Methoxyethyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate; Methyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate; Benzyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate; Benzyl2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate;N-(4-Amino-biphenyl-3-yl)-4-(5-nitro-indazol-2-ylmethyl)-benzamide;N-(2-(4-((2-Aminophenyl)carbamoyl)benzyl)-2H-indazol-5-yl)morpholine-4-carboxamide;5-((2H-Indazol-2-yl)methyl)-N-(2-aminophenyl)thiophene-2-carboxamide;N-(2-Aminophenyl)-5-((5-nitro-2H-indazol-2-yl)methyl)thiophene-2-carboxamide;N-(1-(4-((2-Aminophenyl)carbamoyl)benzyl)-1H-indazol-5-yl)morpholine-4-carboxamide;2-Morpholinoethyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;Pyridin-3-ylmethyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;5-((1H-Indazol-1-yl)methyl)-N-(2-aminophenyl)thiophene-2-carboxamide;4-((2H-Pyrazolo[3,4-b]pyridine-2-yl)methyl)-N-(2-aminophenyl)benzamide;N-(4-Amino-biphenyl-3-yl)-4-pyrazolo[3,4-b]□yridine-2-ylmethyl-benzamide;N-(4-Amino-biphenyl-3-yl)-4-indazol-2-ylmethyl-benzamide;N-(2-Aminophenyl)-4-((3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-Aminophenyl)-4-((3-methyl-2H-indazol-2-yl)methyl)benzamide;4-((1H-indazol-3-ylamino)methyl)-N-(2-aminophenyl)benzamide;4-((1H-pyrazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;N-(2-(4-((2-Aminophenyl)carbamoyl)benzyl)-2H-indazol-5-yl)morpholine-4-carboxamide;Methyl 3-(4-((2H-indazol-2-yl)methyl)benzamido)-4-aminobenzoate;N-(2-aminophenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-fluoro-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-fluoro-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-fluoro-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-fluoro-2H-indazol-2-yl)methyl)benzamide;4-(1-(1H-indazol-1-yl)propan-2-yl)-N-(2-aminophenyl)benzamide;4-(2-(1H-indazol-1-yl)ethyl)-N-(2-aminophenyl)benzamide;4-(2-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((4-chloro-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-chloro-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4,6-difluoro-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4,6-difluoro-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((7-fluoro-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((7-fluoro-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-fluoro-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-fluoro-2H-indazol-2-yl)methyl)benzamide;(R)-4-(1-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide;(S)-4-(1-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((7-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((7-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5,6-difluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5,6-difluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-methoxy-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-methoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-chloro-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-chloro-2H-indazol-2-yl)methyl)benzamide;4-((3-amino-5-(trifluoromethyl)-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;4-((3-amino-5-(trifluoromethyl)-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((3-oxo-2,3-dihydro-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-oxo-1H-indazol-2(3H)-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-methoxy-3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-methoxy-3-methyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-fluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-fluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-ethyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-ethyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-hydroxy-3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-hydroxy-3-methyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-phenyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-phenyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-methoxy-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-methoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3,5-dimethyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3,5-dimethyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((7-methoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-methoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((7-methoxy-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-methoxy-1H-indazol-1-yl)methyl)benzamide;4-((6-acetamido-3-methyl-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;4-((6-acetamido-3-methyl-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((3-amino-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;4-((6-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((6-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((3-methyl-7-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-methyl-6-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-methyl-6-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-methyl-5-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-methyl-5-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;4-((3-amino-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((5-hydroxy-6-methoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5,6-dimethoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5,6-dimethoxy-1H-indazol-1-yl)methyl)benzamide;4-((1H-benzo[d][1,2,3]triazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((2H-benzo[d][1,2,3]triazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;4-((5-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-(piperazin-1-yl)ethyl)-1H-pyrazole-4-carboxamide;4-((2H-indazol-2-yl)methyl)-N-(4-aminopyrimidin-5-yl)benzamide;4-((5-acetamido-3-amino-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((5-acetamido-3-methyl-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;4-((5-acetamido-3-methyl-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-(1-(1H-indazol-1-yl)ethyl)-N-(2-aminophenyl)benzamide;4-(1-(2H-indazol-2-yl)ethyl)-N-(2-aminophenyl)benzamide;5-((5-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)thiophene-2-carboxamide;4-((2H-indazol-2-yl)methyl)-N-(2-amino-5-(thiophen-2-yl)phenyl)benzamide;N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4,6-difluoro-2H-indazol-2-yl)methyl)benzamide;N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4,6-difluoro-1H-indazol-1-yl)methyl)benzamide;N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((6-methoxy-3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide;N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((6-methoxy-3-methyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-(trifluoromethyl)-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-1H-pyrazole-4-carboxylic acid;N-(2-aminophenyl)-4-((3-methyl-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamide;Ethyl 1-(4-(2-aminophenylcarbamoyl)benzyl)-1H-pyrazole-4-carboxylate;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridine-2-ylmethyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-phenyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-benzyl-1H-pyrazole-4-carboxamide;N-(2-aminophenyl)-4-((4,5,6,7-tetrahydro-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4,5,6,7-tetrahydro-1H-indazol-1-yl)methyl)benzamide;4-((1H-pyrazol-3-ylamino)methyl)-N-(2-aminophenyl)benzamide;4-((5-amino-1H-pyrazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((3-amino-1H-pyrazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-methyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-ethyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N,N-dimethyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-isopropyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-cyclopropyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(cyclopropylmethyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-(dimethylamino)ethyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-hydroxyethyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-(dimethylamino)propyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridine-3-ylmethyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridine-4-ylmethyl)-1H-pyrazole-4-carboxamide.;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-morpholinoethyl)-1H-pyrazole-4-carboxamide;N-(2-aminophenyl)-4-((5-methyl-1H-pyrazol-1-yl)methyl)benzamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-propyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-isobutyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-methoxyethyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-methoxypropyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-hydroxypropyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-morpholinopropyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-(piperidin-1-yl)ethyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-(4-methylpiperazin-1-yl)propyl)-1H-pyrazole-4-carboxamide;4-((1H-Pyrrolo[2,3-b]pyridine-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((1H-Indol-3-yl)methyl)-N-(2-aminophenyl)benzamide;4-((1H-indazol-1-yl)methyl)-N-(2-amino-5-fluorophenyl)benzamide;4-((2H-indazol-2-yl)methyl)-N-(2-amino-5-fluorophenyl)benzamide;4-((1H-indazol-1-yl)methyl)-N-(2-amino-5-fluorophenyl)-3-methylbenzamide;4-((2H-indazol-2-yl)methyl)-N-(2-amino-5-fluorophenyl)-3-methylbenzamide;N-(2-aminophenyl)-3-methyl-4-((3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-3-methyl-4-((3-methyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-cyano-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-cyano-2H-indazol-2-yl)methyl)benzamide;1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazole-3-carboxylic acid;2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazole-3-carboxylic acid;N-(2-aminophenyl)-4-((5-cyano-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-cyano-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-(pyridine-2-yl)-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-(pyridine-2-yl)-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-(dimethylamino)-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-(dimethylamino)-2H-indazol-2-yl)methyl)benzamide;4-((1H-indazol-1-yl)methyl)-N-(2-amino-5-(furan-2-yl)phenyl)benzamide;4-((2H-indazol-2-yl)methyl)-N-(2-amino-5-(furan-2-yl)phenyl)benzamide;N-(2-aminophenyl)-4-((3-methoxy-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-methoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-(methoxymethylamino)-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-(methoxymethylamino)-2H-indazol-2-yl)methyl)benzamide;4-((1H-pyrazol-1-yl)methyl)-N-(2-amino-5-fluorophenyl)benzamide;N-(2-amino-5-fluorophenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide;4-((1H-pyrazol-1-yl)methyl)-N-(2-aminophenyl)-3-methylbenzamide;N-(2-amino-5-fluorophenyl)-3-methyl-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-(furan-2-yl)-1H-pyrazol-1-yl)methyl)benzamide;1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-pyrazole-4-carboxylic acid;N-(2-aminophenyl)-4-((3-ethyl-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-ethyl-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-phenyl-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-3-methyl-4-((5-methyl-4-phenyl-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-cyano-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-(pyridine-2-yl)-1H-pyrazol-1-yl)methyl)benzamide;4-((1H-pyrazol-1-yl)methyl)-N-(2-amino-5-(furan-2-yl)phenyl)benzamide;N-(2-amino-5-(furan-2-yl)phenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide;(S)-4-(1-(1H-pyrazol-1-yl)ethyl)-N-(2-aminophenyl)benzamide;(R)-4-(1-(1H-pyrazol-1-yl)ethyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((3-(pyridine-2-yl)-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-methoxy-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-(methoxymethylamino)-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-(methoxymethylamino)-1H-pyrazol-1-yl)methyl)benzamide;and N-(2-aminophenyl)-4-((3-methoxy-1H-pyrazol-1-yl)methyl)benzamide.55. A compound selected from the group consisting of:4-((1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((5-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((5-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((5-nitro-1H-indazol-1-yl)methyl)benzamide;4-((5-benzamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((5-amino-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((5-nitro-2H-indazol-2-yl)methyl)benzamide;4-((5-benzamido-2H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;2-Methoxyethyl2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate; Methyl2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate;2-Methoxyethyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate; Methyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate; Benzyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate; Benzyl2-(4-((2-aminophenyl)carbamoyl)benzyl)-2H-indazol-5-ylcarbamate;N-(4-Amino-biphenyl-3-yl)-4-(5-nitro-indazol-2-ylmethyl)-benzamide;N-(2-(4-((2-Aminophenyl)carbamoyl)benzyl)-2H-indazol-5-yl)morpholine-4-carboxamide;N-(2-Aminophenyl)-5-((5-nitro-2H-indazol-2-yl)methyl)thiophene-2-carboxamide;N-(1-(4-((2-Aminophenyl)carbamoyl)benzyl)-1H-indazol-5-yl)morpholine-4-carboxamide;2-Morpholinoethyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;Pyridin-3-ylmethyl1-(4-((2-aminophenyl)carbamoyl)benzyl)-1H-indazol-5-ylcarbamate;N-(4-Amino-biphenyl-3-yl)-4-pyrazolo[3,4-b]pyridin-2-ylmethyl-benzamide;N-(4-Amino-biphenyl-3-yl)-4-indazol-2-ylmethyl-benzamide;N-(2-aminophenyl)-4-((5-fluoro-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-chloro-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-chloro-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-fluoro-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-methoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((3-chloro-2H-indazol-2-yl)methyl)benzamide;4-((3-amino-5-(trifluoromethyl)-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((6-methoxy-3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-methoxy-3-methyl-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-hydroxy-3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-methoxy-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5-methoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-methoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4-methoxy-1H-indazol-1-yl)methyl)benzamide;4-((6-acetamido-3-methyl-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;4-((6-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((6-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;N-(2-aminophenyl)-4-((3-methyl-5-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5,6-dimethoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5,6-dimethoxy-1H-indazol-1-yl)methyl)benzamide;1-(4-(-(2-aminophenylcarbamoyl)benzyl)-N-(2-(piperazin-1-yl)ethyl)-1H-pyrazole-4-carboxamide;4-((2H-indazol-2-yl)methyl)-N-(2-amino-5-(thiophen-2-yl)phenyl)benzamide;N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4-methyl-1H-pyrazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((6-(trifluoromethyl)-2H-indazol-2-yl)methyl)benzamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridin-2-ylmethyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-phenyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-benzyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-isopropyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-(dimethylamino)propyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridin-3-ylmethyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(pyridin-4-ylmethyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-propyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-isobutyl-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-methoxypropyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-hydroxypropyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(3-morpholinopropyl)-1H-pyrazole-4-carboxamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-(2-(piperidin-1-yl)ethyl)-1H-pyrazole-4-carboxamide;56. A compound selected from the group consisting of:N-(2-aminophenyl)-4-((4,6-difluoro-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((4,6-difluoro-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5,6-difluoro-3-methyl-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5,6-difluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;4-((3-amino-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;4-((6-acetamido-1H-indazol-1-yl)methyl)-N-(2-aminophenyl)benzamide;4-((6-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide;N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4,6-difluoro-2H-indazol-2-yl)methyl)benzamide;N-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4,6-difluoro-1H-indazol-1-yl)methyl)benzamide;1-(4-(2-aminophenylcarbamoyl)benzyl)-N-ethyl-1H-pyrazole-4-carboxamide;N-(2-aminophenyl)-4-((5,6-dimethoxy-1H-indazol-1-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5,6-dimethoxy-2H-indazol-2-yl)methyl)benzamide;andN-(2-aminophenyl)-4-((5-hydroxy-6-methoxy-2H-indazol-2-yl)methyl)benzamide.57. A compound selected from the group consisting of:1-(4-(2-aminophenylcarbamoyl)benzyl)-N-ethyl-1H-pyrazole-4-carboxamide;N-(2-aminophenyl)-4-((5,6-dimethoxy-2H-indazol-2-yl)methyl)benzamide;4-((6-acetamido-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide; and4-((3-amino-2H-indazol-2-yl)methyl)-N-(2-aminophenyl)benzamide.
 58. Acompound selected from the group consisting of:N-(2-aminophenyl)-4-((5-hydroxy-6-methoxy-2H-indazol-2-yl)methyl)benzamide.N-(2-aminophenyl)-4-((5,6-dimethoxy-2H-indazol-2-yl)methyl)benzamide;N-(2-aminophenyl)-4-((5,6-difluoro-3-methyl-2H-indazol-2-yl)methyl)benzamide;andN-(2-amino-5-(thiophen-2-yl)phenyl)-4-((4,6-difluoro-2H-indazol-2-yl)methyl)benzamide.59. The compound according to claim 1, wherein the compound is in theform of a pharmaceutically acceptable salt.
 60. The compound accordingto claim 1, wherein the compound is present in a mixture ofstereoisomers.
 61. The compound according to claim 1, wherein thecompound comprises a single stereoisomer.
 62. A pharmaceuticalcomposition comprising as an active ingredient a compound according toclaim
 1. 63. The pharmaceutical composition according to claim 62,wherein the composition is a solid formulation adapted for oraladministration.
 64. The pharmaceutical composition according to claim62, wherein the composition is a liquid formulation adapted for oraladministration.
 65. The pharmaceutical composition according to claim62, wherein the composition is a tablet.
 66. The pharmaceuticalcomposition according to claim 62, wherein the composition is a liquidformulation adapted for parenteral administration.
 67. A pharmaceuticalcomposition comprising a compound according to claim 1, wherein thecomposition is adapted for administration by a route selected from thegroup consisting of orally, parenterally, intraperitoneally,intravenously, intraarterially, transdermally, sublingually,intramuscularly, rectally, transbuccally, intranasally, liposomally, viainhalation, vaginally, intraoccularly, via local delivery,subcutaneously, intraadiposally, intraarticularly, and intrathecally.68. A kit comprising: a compound according to claim 1; and instructionswhich comprise one or more forms of information selected from the groupconsisting of indicating a disease state for which the compound is to beadministered, storage information for the compound, dosing informationand instructions regarding how to administer the compound.
 69. The kitof claim 68, wherein the kit comprises the compound in a multiple doseform.
 70. An article of manufacture comprising: a compound according toclaim 1; and packaging materials.
 71. The article of manufacture ofclaim 70, wherein the packaging material comprises a container forhousing the compound.
 72. The article of manufacture of claim 71,wherein the container comprises a label indicating one or more membersof the group consisting of a disease state for which the compound is tobe administered, storage information, dosing information and/orinstructions regarding how to administer the compound.
 73. The articleof manufacture of claim 70, wherein the article of manufacture comprisesthe compound in a multiple dose form.
 74. A therapeutic methodcomprising: administering a compound according to claim 1 to a subject.75. A method of inhibiting histone deacetylase comprising: contactinghistone deacetylase with a compound according to claim
 1. 76. The methodaccording to claim 75, wherein the histone deacetylase is a HDAC2. 77.The method according to claim 75, wherein the histone deacetylase is aHDAC8.
 78. A method of inhibiting histone deacetylase comprising:causing a compound according to claim 1 to be present in a subject inorder to inhibit histone deacetylase in vivo.
 79. The method accordingto claim 78, wherein the histone deacetylase is a HDAC2.
 80. The methodaccording to claim 78, wherein the histone deacetylase is a HDAC8.
 81. Amethod of inhibiting histone deacetylase comprising: administering afirst compound to a subject that is converted in vivo to a secondcompound wherein the second compound inhibits histone deacetylase invivo, the second compound being a compound according to claim
 1. 82. Themethod according to claim 81, wherein the histone deacetylase is aHDAC2.
 83. The method according to claim 81, wherein the histonedeacetylase is a HDAC8.
 84. A method of treating a disease state forwhich histone deacetylase possesses activity that contributes to thepathology and/or symptomology of the disease state, the methodcomprising: causing a compound according to claim 1 to be present in asubject in a therapeutically effective amount for the disease state. 85.The method according to claim 84, wherein the histone deacetylase is aHDAC2.
 86. The method according to claim 84, wherein the histonedeacetylase is a HDAC8.
 87. A method of treating a disease state forwhich histone deacetylase possesses activity that contributes to thepathology and/or symptomology of the disease state, the methodcomprising: administering a first compound to a subject that isconverted in vivo to a second compound according to claim 1, wherein thesecond compound is present in a subject in a therapeutically effectiveamount for the disease state.
 88. The method according to claim 87,wherein the histone deacetylase is a HDAC2.
 89. The method according toclaim 87, wherein the histone deacetylase is a HDAC8.
 90. A method oftreating a disease state for which histone deacetylase possessesactivity that contributes to the pathology and/or symptomology of thedisease state, the method comprising: administering a compound accordingto claim 1, wherein the compound is present in the subject in atherapeutically effective amount for the disease state.
 91. The methodaccording to claim 90, wherein the histone deacetylase is a HDAC2. 92.The method according to claim 90, wherein the histone deacetylase is aHDAC8.
 93. A method for treating cancer comprising: administering acomposition according to claim 1 to a mammalian species in need thereof.94. The method of claim 93, wherein the cancer is selected from thegroup consisting of squamous cell carcinoma, astrocytoma, Kaposi'ssarcoma, glioblastoma, non small-cell lung cancer, bladder cancer, headand neck cancer, melanoma, ovarian cancer, prostate cancer, breastcancer, small-cell lung cancer, glioma, colorectal cancer, genitourinarycancer and gastrointestinal cancer.
 95. A method for treatinginflammation, inflammatory bowel disease, psoriasis, or transplantrejection, comprising administering a compound according to claim 1 to amammalian species in need thereof.
 96. A method for treating arthritiscomprising administering a compound according to claim 1 to a mammalianspecies in need thereof.
 97. A method for treating degenerative diseasesof the eye comprising administering a compound according to claim 1 to amammalian species in need thereof.
 98. A method for treating multiplesclerosis, amyotrophic lateral sclerosis, thyroid neoplasm orAlzheimer's disease comprising administering a compound according toclaim 1 to a mammalian species in need thereof.
 99. A method fortreating hyperproliferative skin diseases or inflammatory cutaneousdisorders comprising administering a compound according to claim 1 to amammalian species in need thereof.
 100. A process comprising: reacting acompound comprising the formula

with a compound comprising the formula

under conditions that form a reaction product comprising a formulaselected from the group consisting of

wherein X is a leaving group; A₁ is selected from the group consistingof (C₃₋₁₂)cycloalkyl, hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl,hetero(C₃₋₁₂)bicycloalkyl, aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, andhetero(C₄₋₁₂)bicycloaryl, each substituted or unsubstituted; L is alinker providing a 0-6 atom separation between the two ring atoms towhich L is attached; and R₅, R₆ and R₇ are each independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, oxo, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C4-12)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₆ and R₇ may be takentogether to form a substituted or unsubstituted ring.
 101. The processaccording to claim 100 wherein X is halo.
 102. The process according toclaim 100 wherein X is chloro.
 103. The process according to claim 100wherein X is bromo.
 104. A process comprising: reacting a compoundcomprising the formula

with a compound comprising the formula

under conditions that form a reaction product comprising a formula

wherein n is selected from the group consisting of 0, 1, 2, 3 and 4; A₁is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; R₁ and R₂are each independently selected from the group consisting of hydrogen,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring; R₃ is selected from the groupconsisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; each R₄ is selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and R₅, R₆ and R₇ are each independentlyselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₆ and R₇ may be takentogether to form a substituted or unsubstituted ring.
 105. A processcomprising: reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a reaction product comprising a formula

wherein n is selected from the group consisting of 0, 1, 2, 3 and 4; A₁is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; R₁ and R₂are each independently selected from the group consisting of hydrogen,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl,halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl,sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl,imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring; R₃ is selected from the groupconsisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; each R₄ is selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and R₅, R₆ and R₇ are each independentlyselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₆ and R₇ may be takentogether to form a substituted or unsubstituted ring.
 106. A processcomprising: reacting a compound comprising the formula

with a compound comprising the formulaR—C(O)—X under conditions that form a reaction product comprising aformula

wherein p is selected from the group consisting of 0, 1, 2, 3 and 4; A₁is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; R isselected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; X is a leaving group; R₇ is selected fromthe group consisting of hydrogen, halo, nitro, cyano, oxo, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl,(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and each R₁₂ is independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.
 107. The process accordingto claim 106 wherein X is halo.
 108. The process according to claim 106wherein X is chloro.
 109. The process according to claim 106 wherein Xis bromo.
 110. A process comprising: reacting a compound comprising theformula

with a compound comprising the formulaR—C(O)—X under conditions that form a reaction product comprising aformula

wherein p is selected from the group consisting of 0, 1, 2, 3 and 4; A₁is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; R isselected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; X is a leaving group; R₇ is selected fromthe group consisting of hydrogen, halo, nitro, cyano, oxo, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and each R₁₂ is independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.
 111. The process accordingto claim 110 wherein X is halo.
 112. The process according to claim 110wherein X is chloro.
 113. The process according to claim 110 wherein Xis bromo.
 114. A process comprising: reacting a compound comprising theformula

with a compound comprising the formula

under conditions that form a reaction product comprising a formula

wherein n is selected from the group consisting of 0, 1, 2, 3 and 4; pis selected from the group consisting of 0, 1, 2, 3 and 4; A₁ isselected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; R isselected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; R₁ and R₂ are each independently selectedfrom the group consisting of hydrogen, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring; R₃ is selected from the groupconsisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; each R₄ is selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; R₇ is selected from the group consistingof hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and each R₁₂ is independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.
 115. A process comprising:reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a reaction product comprising a formula

wherein n is selected from the group consisting of 0, 1, 2, 3 and 4; pis selected from the group consisting of 0, 1, 2, 3 and 4; A₁ isselected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; R isselected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; R₁ and R₂ are each independently selectedfrom the group consisting of hydrogen, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino,sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring; R₃ is selected from the groupconsisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; each R₄ is selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; R₇ is selected from the group consistingof hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and each R₁₂ is independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.
 116. A process comprising:reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a first reaction product comprising a formula

reacting the first reaction product with a compound comprising theformula

under conditions that form a second reaction product comprising aformula

wherein n is selected from the group consisting of 0, 1, 2, 3 and 4; Xis a leaving group; A₁ is selected from the group consisting of(C₃₋₁₂)cycloalkyl, hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl,hetero(C₃₋₁₂)bicycloalkyl, aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, andhetero(C₄₋₁₂)bicycloaryl, each substituted or unsubstituted; L is alinker providing a 0-6 atom separation between the two ring atoms towhich L is attached; R₁ and R₂ are each independently selected from thegroup consisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁ and R₂ may be taken together to forma substituted or unsubstituted ring; R₃ is selected from the groupconsisting of hydrogen, hydroxy, alkoxy, aryloxy, heteroaryloxy,carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; each R₄ is selected from the groupconsisting of hydrogen, halo, nitro, cyano, thio, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; R₇ is selected from the group consistingof hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and each R₁₂ is independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.
 117. The process accordingto claim 116 wherein X is halo.
 118. The process according to claim 116wherein X is chloro.
 119. The process according to claim 116 wherein Xis bromo.
 120. The process according to claim 116 comprising: reacting acompound comprising the formula

with a compound comprising the formula

under conditions that form a first reaction product comprising a formula

reacting the first reaction product with a compound comprising theformula

under conditions that form a second reaction product comprising aformula

wherein X is a leaving group.
 121. The process according to claim 120wherein X is halo.
 122. The process according to claim 120 wherein X ischloro.
 123. The process according to claim 120 wherein X is bromo. 124.A compound comprising:

wherein A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; and R₅, R₆and R₇ are each independently selected from the group consisting ofhydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,alkyl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₆ and R₇ may be takentogether to form a substituted or unsubstituted ring.
 125. A compoundcomprising:

wherein A₁ is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; and R₅, R₆and R₇ are each independently selected from the group consisting ofhydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or any two of R₅, R₆ and R₇ may be takentogether to form a substituted or unsubstituted ring.
 126. A compoundcomprising:

wherein p is selected from the group consisting of 0, 1, 2, 3 and 4; A₁is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; R₇ isselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and each R₁₂ is independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.
 127. A compound comprising:

wherein p is selected from the group consisting of 0, 1, 2, 3 and 4; A₁is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; R₇ isselected from the group consisting of hydrogen, halo, nitro, cyano, oxo,thio, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and each R₁₂ is independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.
 128. The compound accordingto claim 127 comprising:


129. A compound comprising:

wherein p is selected from the group consisting of 0, 1, 2, 3 and 4; A₁is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; R isselected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; R₇ is selected from the group consistingof hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and each R₁₂ is independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.
 130. A compound comprising:

wherein p is selected from the group consisting of 0, 1, 2, 3 and 4; A₁is selected from the group consisting of (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl, and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; L is a linker providing a 0-6 atomseparation between the two ring atoms to which L is attached; R isselected from the group consisting of hydrogen, hydroxy, alkoxy,aryloxy, heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, sulfonamido,imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; R₇ is selected from the group consistingof hydrogen, halo, nitro, cyano, oxo, thio, hydroxy, alkoxy, aryloxy,heteroaryloxy, carbonyl, amino, (C₁₋₁₀)alkylamino, amido, carboxamido,sulfonamido, imino, sulfonyl, sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl,carbonyl(C₁₋₃)alkyl, thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl,sulfinyl(C₁₋₃)alkyl, amino (C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl,(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,aryl(C₁₋₁₀)alkyl, heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted; and each R₁₂ is independently selectedfrom the group consisting of hydrogen, halo, nitro, cyano, thio,hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino,(C₁₋₁₀)alkylamino, amido, carboxamido, sulfonamido, imino, sulfonyl,sulfinyl, (C₁₋₁₀)alkyl, halo(C₁₋₁₀)alkyl, carbonyl(C₁₋₃)alkyl,thiocarbonyl(C₁₋₃)alkyl, sulfonyl(C₁₋₃)alkyl, sulfinyl(C₁₋₃)alkyl, amino(C₁₋₁₀)alkyl, imino(C₁₋₃)alkyl, (C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl,hetero(C₃₋₁₂)cycloalkyl(C₁₋₅)alkyl, aryl(C₁₋₁₀)alkyl,heteroaryl(C₁₋₅)alkyl, (C₉₋₁₂)bicycloaryl(C₁₋₅)alkyl,hetero(C₈₋₁₂)bicycloaryl(C₁₋₅)alkyl, (C₃₋₁₂)cycloalkyl,hetero(C₃₋₁₂)cycloalkyl, (C₉₋₁₂)bicycloalkyl, hetero(C₃₋₁₂)bicycloalkyl,aryl, heteroaryl, (C₉₋₁₂)bicycloaryl and hetero(C₄₋₁₂)bicycloaryl, eachsubstituted or unsubstituted, or R₁₂ and R₇ or R₁₁ may be taken togetherto form a substituted or unsubstituted ring.